Porte, Rémi; Belloy, Marcy; Audibert, Alexis; Bassot, Emilie; Aïda, Amel; Alis, Marine; Miranda-Capet, Romain; Jourdes, Aurélie; van Gisbergen, Klaas P J M; Masson, Frédérick; Blanchard, Nicolas Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent infection Journal Article In: Proc Natl Acad Sci U S A, vol. 121, no. 24, pp. e2403054121, 2024, ISSN: 1091-6490. @article{pmid38838017c,
title = {Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent infection},
author = {Rémi Porte and Marcy Belloy and Alexis Audibert and Emilie Bassot and Amel Aïda and Marine Alis and Romain Miranda-Capet and Aurélie Jourdes and Klaas P J M van Gisbergen and Frédérick Masson and Nicolas Blanchard},
doi = {10.1073/pnas.2403054121},
issn = {1091-6490},
year = {2024},
date = {2024-06-01},
journal = {Proc Natl Acad Sci U S A},
volume = {121},
number = {24},
pages = {e2403054121},
abstract = {Chronic infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chronic infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections. |
Porte, Rémi; Belloy, Marcy; Audibert, Alexis; Bassot, Emilie; Aïda, Amel; Alis, Marine; Miranda-Capet, Romain; Jourdes, Aurélie; van Gisbergen, Klaas P J M; Masson, Frédérick; Blanchard, Nicolas Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent infection Journal Article In: Proc Natl Acad Sci U S A, vol. 121, no. 24, pp. e2403054121, 2024, ISSN: 1091-6490. @article{pmid38838017b,
title = {Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent infection},
author = {Rémi Porte and Marcy Belloy and Alexis Audibert and Emilie Bassot and Amel Aïda and Marine Alis and Romain Miranda-Capet and Aurélie Jourdes and Klaas P J M van Gisbergen and Frédérick Masson and Nicolas Blanchard},
doi = {10.1073/pnas.2403054121},
issn = {1091-6490},
year = {2024},
date = {2024-06-01},
urldate = {2024-06-01},
journal = {Proc Natl Acad Sci U S A},
volume = {121},
number = {24},
pages = {e2403054121},
abstract = {Chronic infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chronic infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections. |
Porte, Rémi; Belloy, Marcy; Audibert, Alexis; Bassot, Emilie; Aïda, Amel; Alis, Marine; Miranda-Capet, Romain; Jourdes, Aurélie; van Gisbergen, Klaas P J M; Masson, Frédérick; Blanchard, Nicolas Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent infection Journal Article In: Proc Natl Acad Sci U S A, vol. 121, no. 24, pp. e2403054121, 2024, ISSN: 1091-6490. @article{pmid38838017,
title = {Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent infection},
author = {Rémi Porte and Marcy Belloy and Alexis Audibert and Emilie Bassot and Amel Aïda and Marine Alis and Romain Miranda-Capet and Aurélie Jourdes and Klaas P J M van Gisbergen and Frédérick Masson and Nicolas Blanchard},
doi = {10.1073/pnas.2403054121},
issn = {1091-6490},
year = {2024},
date = {2024-06-01},
journal = {Proc Natl Acad Sci U S A},
volume = {121},
number = {24},
pages = {e2403054121},
abstract = {Chronic infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chronic infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections. |
Mélique, Suzanne; Vadel, Aurélie; Rouquié, Nelly; Yang, Cui; Bories, Cyrielle; Cotineau, Coline; Saoudi, Abdelhadi; Fazilleau, Nicolas; Lesourne, Renaud THEMIS promotes T cell development and maintenance by rising the signaling threshold of the inhibitory receptor BTLA Journal Article In: Proc Natl Acad Sci U S A, vol. 121, no. 20, pp. e2318773121, 2024, ISSN: 1091-6490. @article{pmid38713628,
title = {THEMIS promotes T cell development and maintenance by rising the signaling threshold of the inhibitory receptor BTLA},
author = {Suzanne Mélique and Aurélie Vadel and Nelly Rouquié and Cui Yang and Cyrielle Bories and Coline Cotineau and Abdelhadi Saoudi and Nicolas Fazilleau and Renaud Lesourne},
doi = {10.1073/pnas.2318773121},
issn = {1091-6490},
year = {2024},
date = {2024-05-01},
urldate = {2024-05-01},
journal = {Proc Natl Acad Sci U S A},
volume = {121},
number = {20},
pages = {e2318773121},
abstract = {The current paradigm about the function of T cell immune checkpoints is that these receptors switch on inhibitory signals upon cognate ligand interaction. We here revisit this simple switch model and provide evidence that the T cell lineage protein THEMIS enhances the signaling threshold at which the immune checkpoint BTLA (B- and T-lymphocyte attenuator) represses T cell responses. THEMIS is recruited to the cytoplasmic domain of BTLA and blocks its signaling capacity by promoting/stabilizing the oxidation of the catalytic cysteine of the tyrosine phosphatase SHP-1. In contrast, THEMIS has no detectable effect on signaling pathways regulated by PD-1 (Programmed cell death protein 1), which depend mainly on the tyrosine phosphatase SHP-2. BTLA inhibitory signaling is tuned according to the THEMIS expression level, making CD8+ T cells more resistant to BTLA-mediated inhibition than CD4+ T cells. In the absence of THEMIS, the signaling capacity of BTLA is exacerbated, which results in the attenuation of signals driven by the T cell antigen receptor and by receptors for IL-2 and IL-15, consequently hampering thymocyte positive selection and peripheral CD8+ T cell maintenance. By characterizing the pivotal role of THEMIS in restricting the transmission of BTLA signals, our study suggests that immune checkpoint operability is conditioned by intracellular signal attenuators.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The current paradigm about the function of T cell immune checkpoints is that these receptors switch on inhibitory signals upon cognate ligand interaction. We here revisit this simple switch model and provide evidence that the T cell lineage protein THEMIS enhances the signaling threshold at which the immune checkpoint BTLA (B- and T-lymphocyte attenuator) represses T cell responses. THEMIS is recruited to the cytoplasmic domain of BTLA and blocks its signaling capacity by promoting/stabilizing the oxidation of the catalytic cysteine of the tyrosine phosphatase SHP-1. In contrast, THEMIS has no detectable effect on signaling pathways regulated by PD-1 (Programmed cell death protein 1), which depend mainly on the tyrosine phosphatase SHP-2. BTLA inhibitory signaling is tuned according to the THEMIS expression level, making CD8+ T cells more resistant to BTLA-mediated inhibition than CD4+ T cells. In the absence of THEMIS, the signaling capacity of BTLA is exacerbated, which results in the attenuation of signals driven by the T cell antigen receptor and by receptors for IL-2 and IL-15, consequently hampering thymocyte positive selection and peripheral CD8+ T cell maintenance. By characterizing the pivotal role of THEMIS in restricting the transmission of BTLA signals, our study suggests that immune checkpoint operability is conditioned by intracellular signal attenuators. |
Marrocco, Remi; Bernard, Isabelle; Joulia, Emeline; Barascud, Rebecca; Dejean, Anne S; Lesourne, Renaud; Saoudi, Abdelhadi Positive regulation of Vav1 by Themis controls CD4 T cell pathogenicity in a mouse model of central nervous system inflammation Journal Article In: Cell Mol Life Sci, vol. 81, no. 1, pp. 161, 2024, ISSN: 1420-9071. @article{pmid38565808,
title = {Positive regulation of Vav1 by Themis controls CD4 T cell pathogenicity in a mouse model of central nervous system inflammation},
author = {Remi Marrocco and Isabelle Bernard and Emeline Joulia and Rebecca Barascud and Anne S Dejean and Renaud Lesourne and Abdelhadi Saoudi},
doi = {10.1007/s00018-024-05203-5},
issn = {1420-9071},
year = {2024},
date = {2024-04-01},
urldate = {2024-04-01},
journal = {Cell Mol Life Sci},
volume = {81},
number = {1},
pages = {161},
abstract = {The susceptibility to autoimmune diseases is conditioned by the association of modest genetic alterations which altogether weaken self-tolerance. The mechanism whereby these genetic interactions modulate T-cell pathogenicity remains largely uncovered. Here, we investigated the epistatic interaction of two interacting proteins involved in T Cell Receptor signaling and which were previously associated with the development of Multiple Sclerosis. To this aim, we used mice expressing an hypomorphic variant of Vav1 (Vav1), combined with a T cell-conditional deletion of Themis. We show that the combined mutations in Vav1 and Themis induce a strong attenuation of the severity of Experimental Autoimmune Encephalomyelitis (EAE), contrasting with the moderate effect of the single mutation in each of those two proteins. This genotype-dependent gradual decrease of EAE severity correlates with decreased quantity of phosphorylated Vav1 in CD4 T cells, establishing that Themis promotes the development of encephalitogenic Tconv response by enhancing Vav1 activity. We also show that the cooperative effect of Themis and Vav1 on EAE severity is independent of regulatory T cells and unrelated to the impact of Themis on thymic selection. Rather, it results from decreased production of pro-inflammatory cytokines (IFN-γ, IL-17, TNF and GM-CSF) and reduced T cell infiltration in the CNS. Together, our results provide a rationale to study combination of related genes, in addition to single gene association, to better understand the genetic bases of human diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The susceptibility to autoimmune diseases is conditioned by the association of modest genetic alterations which altogether weaken self-tolerance. The mechanism whereby these genetic interactions modulate T-cell pathogenicity remains largely uncovered. Here, we investigated the epistatic interaction of two interacting proteins involved in T Cell Receptor signaling and which were previously associated with the development of Multiple Sclerosis. To this aim, we used mice expressing an hypomorphic variant of Vav1 (Vav1), combined with a T cell-conditional deletion of Themis. We show that the combined mutations in Vav1 and Themis induce a strong attenuation of the severity of Experimental Autoimmune Encephalomyelitis (EAE), contrasting with the moderate effect of the single mutation in each of those two proteins. This genotype-dependent gradual decrease of EAE severity correlates with decreased quantity of phosphorylated Vav1 in CD4 T cells, establishing that Themis promotes the development of encephalitogenic Tconv response by enhancing Vav1 activity. We also show that the cooperative effect of Themis and Vav1 on EAE severity is independent of regulatory T cells and unrelated to the impact of Themis on thymic selection. Rather, it results from decreased production of pro-inflammatory cytokines (IFN-γ, IL-17, TNF and GM-CSF) and reduced T cell infiltration in the CNS. Together, our results provide a rationale to study combination of related genes, in addition to single gene association, to better understand the genetic bases of human diseases. |
Santamaria, Jérémy C.; Vuillier, Sylvia; Galindo-Albarrán, Ariel O.; Castan, Sarah; Detraves, Claire; Joffre, Olivier P.; Romagnoli, Paola; van Meerwijk, Joost P. M. The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse Journal Article In: Front. Immunol., vol. 15, 2024, ISSN: 1664-3224. @article{Santamaria2024,
title = {The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse},
author = {Jérémy C. Santamaria and Sylvia Vuillier and Ariel O. Galindo-Albarrán and Sarah Castan and Claire Detraves and Olivier P. Joffre and Paola Romagnoli and Joost P. M. van Meerwijk},
doi = {10.3389/fimmu.2024.1358459},
issn = {1664-3224},
year = {2024},
date = {2024-02-09},
journal = {Front. Immunol.},
volume = {15},
publisher = {Frontiers Media SA},
abstract = {Regulatory T lymphocytes expressing the transcription factor Foxp3 (Tregs) play an important role in the prevention of autoimmune diseases and other immunopathologies. Aberrations in Treg-mediated immunosuppression are therefore thought to be involved in the development of autoimmune pathologies, but few have been documented. Recent reports indicated a central role for Tregs developing during the neonatal period in the prevention of autoimmune pathology. We therefore investigated the development of Tregs in neonatal NOD mice, an important animal model for autoimmune type 1 diabetes. Surprisingly, we found that, as compared with seven other commonly studied inbred mouse strains, in neonatal NOD mice, exceptionally large proportions of developing Tregs express high levels of GITR and PD-1. The latter phenotype was previously associated with high Treg autoreactivity in C57BL/6 mice, which we here confirm for NOD animals. The proportions of newly developing GITRhighPD-1+ Tregs rapidly drop during the first week of age. A genome-wide genetic screen indicated the involvement of several diabetes susceptibility loci in this trait. Analysis of a congenic mouse strain confirmed that Idd5 contributes to the genetic control of GITRhighPD-1+ Treg development in neonates. Our data thus demonstrate an intriguing and paradoxical correlation between an idiosyncrasy in Treg development in NOD mice and their susceptibility to type 1 diabetes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Regulatory T lymphocytes expressing the transcription factor Foxp3 (Tregs) play an important role in the prevention of autoimmune diseases and other immunopathologies. Aberrations in Treg-mediated immunosuppression are therefore thought to be involved in the development of autoimmune pathologies, but few have been documented. Recent reports indicated a central role for Tregs developing during the neonatal period in the prevention of autoimmune pathology. We therefore investigated the development of Tregs in neonatal NOD mice, an important animal model for autoimmune type 1 diabetes. Surprisingly, we found that, as compared with seven other commonly studied inbred mouse strains, in neonatal NOD mice, exceptionally large proportions of developing Tregs express high levels of GITR and PD-1. The latter phenotype was previously associated with high Treg autoreactivity in C57BL/6 mice, which we here confirm for NOD animals. The proportions of newly developing GITRhighPD-1+ Tregs rapidly drop during the first week of age. A genome-wide genetic screen indicated the involvement of several diabetes susceptibility loci in this trait. Analysis of a congenic mouse strain confirmed that Idd5 contributes to the genetic control of GITRhighPD-1+ Treg development in neonates. Our data thus demonstrate an intriguing and paradoxical correlation between an idiosyncrasy in Treg development in NOD mice and their susceptibility to type 1 diabetes. |
Joulia, Emeline; Michieletto, Michaël F.; Agesta, Arantxa; Peillex, Cindy; Girault, Virginie; Dorze, Anne-Louise Le; Peroceschi, Romain; Bucciarelli, Florence; Szelechowski, Marion; Chaubet, Adeline; Hakim, Nawad; Marrocco, Rémi; Lhuillier, Emeline; Lebeurrier, Manuel; Argüello, Rafael J.; Saoudi, Abdelhadi; Costa, Hicham El; Adoue, Veronique; Walzer, Thierry; Sarry, Jean-Emmanuel; Dejean, Anne S. Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation Journal Article In: vol. 221, no. 2, 2024, ISSN: 1540-9538. @article{Joulia2024,
title = {Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation},
author = {Emeline Joulia and Michaël F. Michieletto and Arantxa Agesta and Cindy Peillex and Virginie Girault and Anne-Louise Le Dorze and Romain Peroceschi and Florence Bucciarelli and Marion Szelechowski and Adeline Chaubet and Nawad Hakim and Rémi Marrocco and Emeline Lhuillier and Manuel Lebeurrier and Rafael J. Argüello and Abdelhadi Saoudi and Hicham El Costa and Veronique Adoue and Thierry Walzer and Jean-Emmanuel Sarry and Anne S. Dejean},
doi = {10.1084/jem.20230449},
issn = {1540-9538},
year = {2024},
date = {2024-02-05},
volume = {221},
number = {2},
publisher = {Rockefeller University Press},
abstract = {The mechanisms whereby Eomes controls tissue accumulation of T cells and strengthens inflammation remain ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. While Eomes is dispensable for the initial priming of CD4+ T cells, it is required for long-term maintenance of CNS-infiltrating CD4+ T cells. We reveal that the impact of Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and functions. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in CD4+ T cells from healthy donors and multiple sclerosis patients. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The mechanisms whereby Eomes controls tissue accumulation of T cells and strengthens inflammation remain ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. While Eomes is dispensable for the initial priming of CD4+ T cells, it is required for long-term maintenance of CNS-infiltrating CD4+ T cells. We reveal that the impact of Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and functions. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in CD4+ T cells from healthy donors and multiple sclerosis patients. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death. |
Joulia, Emeline; Michieletto, Michaël F; Agesta, Arantxa; Peillex, Cindy; Girault, Virginie; Dorze, Anne-Louise Le; Peroceschi, Romain; Bucciarelli, Florence; Szelechowski, Marion; Chaubet, Adeline; Hakim, Nawad; Marrocco, Rémi; Lhuillier, Emeline; Lebeurrier, Manuel; Argüello, Rafael J; Saoudi, Abdelhadi; Costa, Hicham El; Adoue, Veronique; Walzer, Thierry; Sarry, Jean-Emmanuel; Dejean, Anne S Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation Journal Article In: J Exp Med, vol. 221, no. 2, 2024, ISSN: 1540-9538. @article{pmid38189779,
title = {Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation},
author = {Emeline Joulia and Michaël F Michieletto and Arantxa Agesta and Cindy Peillex and Virginie Girault and Anne-Louise Le Dorze and Romain Peroceschi and Florence Bucciarelli and Marion Szelechowski and Adeline Chaubet and Nawad Hakim and Rémi Marrocco and Emeline Lhuillier and Manuel Lebeurrier and Rafael J Argüello and Abdelhadi Saoudi and Hicham El Costa and Veronique Adoue and Thierry Walzer and Jean-Emmanuel Sarry and Anne S Dejean},
doi = {10.1084/jem.20230449},
issn = {1540-9538},
year = {2024},
date = {2024-02-01},
urldate = {2024-02-01},
journal = {J Exp Med},
volume = {221},
number = {2},
abstract = {The mechanisms whereby Eomes controls tissue accumulation of T cells and strengthens inflammation remain ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. While Eomes is dispensable for the initial priming of CD4+ T cells, it is required for long-term maintenance of CNS-infiltrating CD4+ T cells. We reveal that the impact of Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and functions. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in CD4+ T cells from healthy donors and multiple sclerosis patients. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The mechanisms whereby Eomes controls tissue accumulation of T cells and strengthens inflammation remain ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. While Eomes is dispensable for the initial priming of CD4+ T cells, it is required for long-term maintenance of CNS-infiltrating CD4+ T cells. We reveal that the impact of Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and functions. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in CD4+ T cells from healthy donors and multiple sclerosis patients. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death. |
Kari, Saniya; Bucciarelli, Florence; Angles, Thibault; Oster, Anne-Cecile; Cauboue, Pauline; Laviolette, Karl; Mougenot, Madeline; Morandi, Elena; Bernard, Isabelle; Pignolet, Beatrice; Bost, Chloé; Thomas, Joelle; Nogueira, Leonor; Saoudi, Abdelhadi; Liblau, Roland; Astier, Anne L Increased levels of circulating soluble CD226 in multiple sclerosis Journal Article In: Mult Scler, pp. 13524585241234489, 2024, ISSN: 1477-0970. @article{pmid38424741,
title = {Increased levels of circulating soluble CD226 in multiple sclerosis},
author = {Saniya Kari and Florence Bucciarelli and Thibault Angles and Anne-Cecile Oster and Pauline Cauboue and Karl Laviolette and Madeline Mougenot and Elena Morandi and Isabelle Bernard and Beatrice Pignolet and Chloé Bost and Joelle Thomas and Leonor Nogueira and Abdelhadi Saoudi and Roland Liblau and Anne L Astier},
doi = {10.1177/13524585241234489},
issn = {1477-0970},
year = {2024},
date = {2024-02-01},
urldate = {2024-02-01},
journal = {Mult Scler},
pages = {13524585241234489},
abstract = {BACKGROUND: The glycoprotein CD226 plays a key role in regulating immune cell function. Soluble CD226 (sCD226) is increased in sera of patients with several chronic inflammatory diseases but its levels in neuroinflammatory diseases such as multiple sclerosis (MS) are unknown.nnOBJECTIVE: To investigate the presence and functional implications of sCD226 in persons with multiple sclerosis (pwMS) and other neurological diseases.nnMETHODS: The mechanisms of sCD226 production were first investigated by analyzing CD226 surface expression levels and supernatants of CD3/CD226-coactivated T cells. The role of sCD226 on dendritic cell maturation was evaluated. The concentration of sCD226 in the sera from healthy donors (HD), pwMS, neuromyelitis optica (NMO), and Alzheimer's disease (AD) was measured.nnRESULTS: CD3/CD226-costimulation induced CD226 shedding. Addition of sCD226 to dendritic cells during their maturation led to an increased production of the pro-inflammatory cytokine interleukin (IL)-23. We observed a significant increase in sCD226 in sera from pwMS and NMO compared to HD and AD. In MS, levels were increased in both relapsing-remitting multiple sclerosis (RRMS) and secondary-progressive multiple sclerosis (SPMS) compared to clinically isolated syndrome (CIS).nnCONCLUSION: Our data suggest that T-cell activation leads to release of sCD226 that could promote inflammation and raises the possibility of using sCD226 as a biomarker for neuroinflammation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The glycoprotein CD226 plays a key role in regulating immune cell function. Soluble CD226 (sCD226) is increased in sera of patients with several chronic inflammatory diseases but its levels in neuroinflammatory diseases such as multiple sclerosis (MS) are unknown.nnOBJECTIVE: To investigate the presence and functional implications of sCD226 in persons with multiple sclerosis (pwMS) and other neurological diseases.nnMETHODS: The mechanisms of sCD226 production were first investigated by analyzing CD226 surface expression levels and supernatants of CD3/CD226-coactivated T cells. The role of sCD226 on dendritic cell maturation was evaluated. The concentration of sCD226 in the sera from healthy donors (HD), pwMS, neuromyelitis optica (NMO), and Alzheimer's disease (AD) was measured.nnRESULTS: CD3/CD226-costimulation induced CD226 shedding. Addition of sCD226 to dendritic cells during their maturation led to an increased production of the pro-inflammatory cytokine interleukin (IL)-23. We observed a significant increase in sCD226 in sera from pwMS and NMO compared to HD and AD. In MS, levels were increased in both relapsing-remitting multiple sclerosis (RRMS) and secondary-progressive multiple sclerosis (SPMS) compared to clinically isolated syndrome (CIS).nnCONCLUSION: Our data suggest that T-cell activation leads to release of sCD226 that could promote inflammation and raises the possibility of using sCD226 as a biomarker for neuroinflammation. |
Welsh, Joshua A.; Goberdhan, Deborah C. I.; O'Driscoll, Lorraine; Buzas, Edit I.; Blenkiron, Cherie; Bussolati, Benedetta; Cai, Houjian; Vizio, Dolores Di; Driedonks, Tom A. P.; Erdbrügger, Uta; Falcon‐Perez, Juan M.; Fu, Qing‐Ling; Hill, Andrew F.; Lenassi, Metka; Lim, Sai Kiang; Mahoney, Mỹ G.; Mohanty, Sujata; Möller, Andreas; Nieuwland, Rienk; Ochiya, Takahiro; Sahoo, Susmita; Torrecilhas, Ana C.; Zheng, Lei; Zijlstra, Andries; Abuelreich, Sarah; Bagabas, Reem; Bergese, Paolo; Bridges, Esther M.; Brucale, Marco; Burger, Dylan; Carney, Randy P.; Cocucci, Emanuele; Crescitelli, Rossella; Hanser, Edveena; Harris, Adrian L.; Haughey, Norman J.; Hendrix, An; Ivanov, Alexander R.; Jovanovic‐Talisman, Tijana; Kruh‐Garcia, Nicole A.; Faustino, Vroniqa Ku'ulei‐Lyn; Kyburz, Diego; Lässer, Cecilia; Lennon, Kathleen M.; Lötvall, Jan; Maddox, Adam L.; Martens‐Uzunova, Elena S.; Mizenko, Rachel R.; Newman, Lauren A.; Ridolfi, Andrea; Rohde, Eva; Rojalin, Tatu; Rowland, Andrew; Saftics, Andras; Sandau, Ursula S.; Saugstad, Julie A.; Shekari, Faezeh; Swift, Simon; Ter‐Ovanesyan, Dmitry; Tosar, Juan P.; Useckaite, Zivile; Valle, Francesco; Varga, Zoltan; van der Pol, Edwin; van Herwijnen, Martijn J. C.; Wauben, Marca H. M.; Wehman, Ann M.; Williams, Sarah; Zendrini, Andrea; Zimmerman, Alan J.; and Clotilde Théry,; Witwer, Kenneth W. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches Journal Article In: J of Extracellular Vesicle, vol. 13, no. 2, 2024, ISSN: 2001-3078. @article{Welsh2024,
title = {Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches},
author = {Joshua A. Welsh and Deborah C. I. Goberdhan and Lorraine O'Driscoll and Edit I. Buzas and Cherie Blenkiron and Benedetta Bussolati and Houjian Cai and Dolores Di Vizio and Tom A. P. Driedonks and Uta Erdbrügger and Juan M. Falcon‐Perez and Qing‐Ling Fu and Andrew F. Hill and Metka Lenassi and Sai Kiang Lim and Mỹ G. Mahoney and Sujata Mohanty and Andreas Möller and Rienk Nieuwland and Takahiro Ochiya and Susmita Sahoo and Ana C. Torrecilhas and Lei Zheng and Andries Zijlstra and Sarah Abuelreich and Reem Bagabas and Paolo Bergese and Esther M. Bridges and Marco Brucale and Dylan Burger and Randy P. Carney and Emanuele Cocucci and Rossella Crescitelli and Edveena Hanser and Adrian L. Harris and Norman J. Haughey and An Hendrix and Alexander R. Ivanov and Tijana Jovanovic‐Talisman and Nicole A. Kruh‐Garcia and Vroniqa Ku'ulei‐Lyn Faustino and Diego Kyburz and Cecilia Lässer and Kathleen M. Lennon and Jan Lötvall and Adam L. Maddox and Elena S. Martens‐Uzunova and Rachel R. Mizenko and Lauren A. Newman and Andrea Ridolfi and Eva Rohde and Tatu Rojalin and Andrew Rowland and Andras Saftics and Ursula S. Sandau and Julie A. Saugstad and Faezeh Shekari and Simon Swift and Dmitry Ter‐Ovanesyan and Juan P. Tosar and Zivile Useckaite and Francesco Valle and Zoltan Varga and Edwin van der Pol and Martijn J. C. van Herwijnen and Marca H. M. Wauben and Ann M. Wehman and Sarah Williams and Andrea Zendrini and Alan J. Zimmerman and and Clotilde Théry and Kenneth W. Witwer},
doi = {10.1002/jev2.12404},
issn = {2001-3078},
year = {2024},
date = {2024-02-00},
urldate = {2024-02-00},
journal = {J of Extracellular Vesicle},
volume = {13},
number = {2},
publisher = {Wiley},
abstract = {<jats:title>Abstract</jats:title><jats:p>Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year‐on‐year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non‐vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.</jats:p>},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
<jats:title>Abstract</jats:title><jats:p>Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year‐on‐year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non‐vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.</jats:p> |
Joulia, Emeline; Michieletto, Michaël F.; Agesta, Arantxa; Peillex, Cindy; Girault, Virginie; Dorze, Anne-Louise Le; Peroceschi, Romain; Bucciarelli, Florence; Szelechowski, Marion; Chaubet, Adeline; Hakim, Nawad; Marrocco, Rémi; Lhuillier, Emeline; Lebeurrier, Manuel; Argüello, Rafael J.; Saoudi, Abdelhadi; Costa, Hicham El; Adoue, Veronique; Walzer, Thierry; Sarry, Jean-Emmanuel; Dejean, Anne S. Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation Journal Article In: Journal of Experimental Medicine, vol. 221, no. 2, 2024, ISSN: 0022-1007. @article{nokey,
title = {Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation},
author = {Emeline Joulia and Michaël F. Michieletto and Arantxa Agesta and Cindy Peillex and Virginie Girault and Anne-Louise Le Dorze and Romain Peroceschi and Florence Bucciarelli and Marion Szelechowski and Adeline Chaubet and Nawad Hakim and Rémi Marrocco and Emeline Lhuillier and Manuel Lebeurrier and Rafael J. Argüello and Abdelhadi Saoudi and Hicham El Costa and Veronique Adoue and Thierry Walzer and Jean-Emmanuel Sarry and Anne S. Dejean},
doi = {10.1084/jem.20230449},
issn = {0022-1007},
year = {2024},
date = {2024-01-08},
journal = {Journal of Experimental Medicine},
volume = {221},
number = {2},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Vellas, C.; Nayrac, M.; Collercandy, N.; Requena, M.; Jeanne, N.; Latour, J.; Dimeglio, C.; Cazabat, M.; Barange, K.; Alric, L.; Carrere, N.; Martin-Blondel, G.; Izopet, J.; Delobel, P. Intact proviruses are enriched in the colon and associated with PD-1(+)TIGIT(-) mucosal CD4(+) T cells of people with HIV-1 on antiretroviral therapy Journal Article In: EBioMedicine, vol. 100, pp. 104954, 2024, ISSN: 2352-3964 (Electronic) 2352-3964 (Linking). @article{RN27e,
title = {Intact proviruses are enriched in the colon and associated with PD-1(+)TIGIT(-) mucosal CD4(+) T cells of people with HIV-1 on antiretroviral therapy},
author = {C. Vellas and M. Nayrac and N. Collercandy and M. Requena and N. Jeanne and J. Latour and C. Dimeglio and M. Cazabat and K. Barange and L. Alric and N. Carrere and G. Martin-Blondel and J. Izopet and P. Delobel},
url = {https://www.ncbi.nlm.nih.gov/pubmed/38160480},
doi = {10.1016/j.ebiom.2023.104954},
issn = {2352-3964 (Electronic) 2352-3964 (Linking)},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {EBioMedicine},
volume = {100},
pages = {104954},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Vellas, C.; Martres, D.; Requena, M.; Nayrac, M.; Collercandy, N.; Latour, J.; Barange, K.; Alric, L.; Martin-Blondel, G.; Izopet, J.; Lagane, B.; Delobel, P. Compartmentalized HIV-1 reservoir in intestinal monocytes/macrophages on antiretroviral therapy Journal Article In: J Infect Dis, 2024, ISSN: 1537-6613 (Electronic) 0022-1899 (Linking). @article{RN26q,
title = {Compartmentalized HIV-1 reservoir in intestinal monocytes/macrophages on antiretroviral therapy},
author = {C. Vellas and D. Martres and M. Requena and M. Nayrac and N. Collercandy and J. Latour and K. Barange and L. Alric and G. Martin-Blondel and J. Izopet and B. Lagane and P. Delobel},
url = {https://www.ncbi.nlm.nih.gov/pubmed/39561178},
doi = {10.1093/infdis/jiae557},
issn = {1537-6613 (Electronic) 0022-1899 (Linking)},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {J Infect Dis},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Paronetto, O.; Allioux, C.; Dimeglio, C.; Lobjois, L.; Jeanne, N.; Ranger, N.; Boineau, J.; Pucelle, M.; Demmou, S.; Abravanel, F.; Chapuy-Regaud, S.; Izopet, J.; Lhomme, S. Characterization of virus‒host recombinant variants of the hepatitis E virus Journal Article In: J Virol, vol. 98, no. 6, pp. e0029524, 2024, ISSN: 1098-5514 (Electronic) 0022-538X (Linking). @article{RN4510,
title = {Characterization of virus‒host recombinant variants of the hepatitis E virus},
author = {O. Paronetto and C. Allioux and C. Dimeglio and L. Lobjois and N. Jeanne and N. Ranger and J. Boineau and M. Pucelle and S. Demmou and F. Abravanel and S. Chapuy-Regaud and J. Izopet and S. Lhomme},
url = {https://www.ncbi.nlm.nih.gov/pubmed/38712945},
doi = {10.1128/jvi.00295-24},
issn = {1098-5514 (Electronic) 0022-538X (Linking)},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {J Virol},
volume = {98},
number = {6},
pages = {e0029524},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Briand-Mésange, Fabienne; Gennero, Isabelle; Salles, Juliette; Trudel, Stéphanie; Dahan, Lionel; Ausseil, Jérôme; Payrastre, Bernard; Salles, Jean Pierre; Chap, Hugues From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling Journal Article In: Molecules, vol. 29, no. 15, 2024, ISSN: 14203049. @article{Briand-Mesange2024,
title = {From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling},
author = {Fabienne Briand-Mésange and Isabelle Gennero and Juliette Salles and Stéphanie Trudel and Lionel Dahan and Jérôme Ausseil and Bernard Payrastre and Jean Pierre Salles and Hugues Chap},
doi = {10.3390/molecules29153694},
issn = {14203049},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Molecules},
volume = {29},
number = {15},
abstract = {2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid (EC), acting as a full agonist at both CB1 and CB2 cannabinoid receptors. It is synthesized on demand in postsynaptic membranes through the sequential action of phosphoinositide-specific phospholipase Cβ1 (PLCβ1) and diacylglycerol lipase α (DAGLα), contributing to retrograde signaling upon interaction with presynaptic CB1. However, 2-AG production might also involve various combinations of PLC and DAGL isoforms, as well as additional intracellular pathways implying other enzymes and substrates. Three other alternative pathways of 2-AG synthesis rest on the extracellular cleavage of 2-arachidonoyl-lysophospholipids by three different hydrolases: glycerophosphodiesterase 3 (GDE3), lipid phosphate phosphatases (LPPs), and two members of ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPP6–7). We propose the names of AlterAG-1, -2, and -3 for three pathways sharing an ectocellular localization, allowing them to convert extracellular lysophospholipid mediators into 2-AG, thus inducing typical signaling switches between various G-protein-coupled receptors (GPCRs). This implies the critical importance of the regioisomerism of both lysophospholipid (LPLs) and 2-AG, which is the object of deep analysis within this review. The precise functional roles of AlterAGs are still poorly understood and will require gene invalidation approaches, knowing that both 2-AG and its related lysophospholipids are involved in numerous aspects of physiology and pathology, including cancer, inflammation, immune defenses, obesity, bone development, neurodegeneration, or psychiatric disorders.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid (EC), acting as a full agonist at both CB1 and CB2 cannabinoid receptors. It is synthesized on demand in postsynaptic membranes through the sequential action of phosphoinositide-specific phospholipase Cβ1 (PLCβ1) and diacylglycerol lipase α (DAGLα), contributing to retrograde signaling upon interaction with presynaptic CB1. However, 2-AG production might also involve various combinations of PLC and DAGL isoforms, as well as additional intracellular pathways implying other enzymes and substrates. Three other alternative pathways of 2-AG synthesis rest on the extracellular cleavage of 2-arachidonoyl-lysophospholipids by three different hydrolases: glycerophosphodiesterase 3 (GDE3), lipid phosphate phosphatases (LPPs), and two members of ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPP6–7). We propose the names of AlterAG-1, -2, and -3 for three pathways sharing an ectocellular localization, allowing them to convert extracellular lysophospholipid mediators into 2-AG, thus inducing typical signaling switches between various G-protein-coupled receptors (GPCRs). This implies the critical importance of the regioisomerism of both lysophospholipid (LPLs) and 2-AG, which is the object of deep analysis within this review. The precise functional roles of AlterAGs are still poorly understood and will require gene invalidation approaches, knowing that both 2-AG and its related lysophospholipids are involved in numerous aspects of physiology and pathology, including cancer, inflammation, immune defenses, obesity, bone development, neurodegeneration, or psychiatric disorders. |
Huret, C.; Ferraye, L.; David, A.; Mohamed, M.; Valentin, N.; Charlotte, F.; Savignac, M.; Goodhardt, M.; Guery, J. C.; Rougeulle, C.; Morey, C. Altered X-chromosome inactivation predisposes to autoimmunity Journal Article In: Sci Adv, vol. 10, no. 18, pp. eadn6537, 2024, ISSN: 2375-2548 (Electronic) 2375-2548 (Linking). @article{RN2487,
title = {Altered X-chromosome inactivation predisposes to autoimmunity},
author = {Huret, C. and Ferraye, L. and David, A. and Mohamed, M. and Valentin, N. and Charlotte, F. and Savignac, M. and Goodhardt, M. and Guery, J. C. and Rougeulle, C. and Morey, C.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/38701219},
doi = {10.1126/sciadv.adn6537},
issn = {2375-2548 (Electronic) 2375-2548 (Linking)},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Sci Adv},
volume = {10},
number = {18},
pages = {eadn6537},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Chi, L.; Liu, C.; Gribonika, I.; Gschwend, J.; Corral, D.; Han, S. J.; Lim, A. I.; Rivera, C. A.; Link, V. M.; Wells, A. C.; Bouladoux, N.; Collins, N.; Lima-Junior, D. S.; Enamorado, M.; Rehermann, B.; Laffont, S.; Guery, J. C.; Tussiwand, R.; Schneider, C.; Belkaid, Y. Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis Journal Article In: Science, vol. 384, no. 6692, pp. eadk6200, 2024, ISSN: 1095-9203 (Electronic) 0036-8075 (Linking). @article{RN2480,
title = {Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis},
author = {Chi, L. and Liu, C. and Gribonika, I. and Gschwend, J. and Corral, D. and Han, S. J. and Lim, A. I. and Rivera, C. A. and Link, V. M. and Wells, A. C. and Bouladoux, N. and Collins, N. and Lima-Junior, D. S. and Enamorado, M. and Rehermann, B. and Laffont, S. and Guery, J. C. and Tussiwand, R. and Schneider, C. and Belkaid, Y.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/38574174},
doi = {10.1126/science.adk6200},
issn = {1095-9203 (Electronic) 0036-8075 (Linking)},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Science},
volume = {384},
number = {6692},
pages = {eadk6200},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Degboe, Y.; Severino-Freire, M.; Couture, G.; Apoil, P. A.; Gaudenzio, N.; Hermine, O.; Ruyssen-Witrand, A.; Paul, C.; Laroche, M.; Constantin, A.; Livideanu, C. B. The Prevalence Of Osteoporosis Is Low in Adult Cutaneous Mastocytosis Patients Journal Article In: J Allergy Clin Immunol Pract, vol. 12, no. 5, pp. 1306-1312, 2024, ISSN: 2213-2201 (Electronic), (Degboe, Yannick
Severino-Freire, Maella
Couture, Guillaume
Apoil, Pol-Andre
Gaudenzio, Nicolas
Hermine, Olivier
Ruyssen-Witrand, Adeline
Paul, Carle
Laroche, Michel
Constantin, Arnaud
Livideanu, Cristina Bulai
eng
Research Support, Non-U.S. Gov't
2024/03/01
J Allergy Clin Immunol Pract. 2024 May;12(5):1306-1312. doi: 10.1016/j.jaip.2024.02.021. Epub 2024 Feb 27.). @article{RN2122,
title = {The Prevalence Of Osteoporosis Is Low in Adult Cutaneous Mastocytosis Patients},
author = {Y. Degboe and M. Severino-Freire and G. Couture and P. A. Apoil and N. Gaudenzio and O. Hermine and A. Ruyssen-Witrand and C. Paul and M. Laroche and A. Constantin and C. B. Livideanu},
url = {https://www.ncbi.nlm.nih.gov/pubmed/38423295},
doi = {10.1016/j.jaip.2024.02.021},
issn = {2213-2201 (Electronic)},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {J Allergy Clin Immunol Pract},
volume = {12},
number = {5},
pages = {1306-1312},
abstract = {BACKGROUND: Systemic mastocytosis (SM) is a clonal disorder of mast cells (MCs) frequently associated with vertebral osteoporosis (OP) and subsequent vertebral fractures (VFs). The natural history of this OP remains unclear. Importantly, we do not know whether OP represents an early event triggered alongside MC abnormalities, and whether MC clonality is sufficient to trigger osteoporosis. OBJECTIVE: To describe OP in patients with medullar clonality in cutaneous mastocytosis (CM) and monoclonal mast cell activation syndrome (MMAS) and to compare their osteoporosis characteristics with those of nonadvanced SM patients (bone marrow mastocytosis and indolent systemic mastocytosis). METHODS: We retrospectively analyzed clinical, biological, and densitometric data of 27 CM, 13 MMAS, and 135 SM patients from the Mastocytosis Expert Center (CEREMAST) in Toulouse, France. RESULTS: The OP (respectively 3.7, 30.8, and 34.1%) and VFs (0.0%, 15.4%, and 20%) were less frequent in CM than in MMAS and SM, despite the presence of clonal MCs in the bone marrow. Most patients with OP and VFs in the non-SM groups had the usual risk factors for OP. Interestingly, the only non-SM patient with a typical SM-like OP had high bone marrow tryptase, developed bone marrow KIT mutation during follow-up, and had a family history of SM. Our data show that OP is not a common clinical finding in CM but is frequent in MMAS. When OP and VFs occur in CM and MMAS patients, they differ from the usual phenotype of SM bone fragility. CONCLUSIONS: Our findings suggest that, in most CM patients, the meaning and management of OP differs from that of OP in MMAS and nonadvanced SM. Prospective longitudinal studies and the validation of predictors are needed to identify CM and MMAS patients developing SM-related OP.},
note = {Degboe, Yannick
Severino-Freire, Maella
Couture, Guillaume
Apoil, Pol-Andre
Gaudenzio, Nicolas
Hermine, Olivier
Ruyssen-Witrand, Adeline
Paul, Carle
Laroche, Michel
Constantin, Arnaud
Livideanu, Cristina Bulai
eng
Research Support, Non-U.S. Gov't
2024/03/01
J Allergy Clin Immunol Pract. 2024 May;12(5):1306-1312. doi: 10.1016/j.jaip.2024.02.021. Epub 2024 Feb 27.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Systemic mastocytosis (SM) is a clonal disorder of mast cells (MCs) frequently associated with vertebral osteoporosis (OP) and subsequent vertebral fractures (VFs). The natural history of this OP remains unclear. Importantly, we do not know whether OP represents an early event triggered alongside MC abnormalities, and whether MC clonality is sufficient to trigger osteoporosis. OBJECTIVE: To describe OP in patients with medullar clonality in cutaneous mastocytosis (CM) and monoclonal mast cell activation syndrome (MMAS) and to compare their osteoporosis characteristics with those of nonadvanced SM patients (bone marrow mastocytosis and indolent systemic mastocytosis). METHODS: We retrospectively analyzed clinical, biological, and densitometric data of 27 CM, 13 MMAS, and 135 SM patients from the Mastocytosis Expert Center (CEREMAST) in Toulouse, France. RESULTS: The OP (respectively 3.7, 30.8, and 34.1%) and VFs (0.0%, 15.4%, and 20%) were less frequent in CM than in MMAS and SM, despite the presence of clonal MCs in the bone marrow. Most patients with OP and VFs in the non-SM groups had the usual risk factors for OP. Interestingly, the only non-SM patient with a typical SM-like OP had high bone marrow tryptase, developed bone marrow KIT mutation during follow-up, and had a family history of SM. Our data show that OP is not a common clinical finding in CM but is frequent in MMAS. When OP and VFs occur in CM and MMAS patients, they differ from the usual phenotype of SM bone fragility. CONCLUSIONS: Our findings suggest that, in most CM patients, the meaning and management of OP differs from that of OP in MMAS and nonadvanced SM. Prospective longitudinal studies and the validation of predictors are needed to identify CM and MMAS patients developing SM-related OP. |
Portillo, D. Caillet; Puechal, X.; Masson, M.; Kostine, M.; Michaut, A.; Ramon, A.; Wendling, D.; Costedoat-Chalumeau, N.; Richette, P.; Marotte, H.; Vix-Portet, J.; Dubost, J. J.; Ottaviani, S.; Mouterde, G.; Grasland, A.; Frazier, A.; Germain, V.; Coury, F.; Tournadre, A.; Soubrier, M.; Cavalie, L.; Brevet, P.; Zabraniecki, L.; Jamard, B.; Couture, G.; Arnaud, L.; Richez, C.; Degboe, Y.; Ruyssen-Witrand, A.; Constantin, A. Diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease: Data from the French Tw-IRD registry Journal Article In: J Infect, vol. 88, no. 2, pp. 132-138, 2024, ISSN: 1532-2742 (Electronic) 0163-4453 (Linking), (Caillet Portillo, Damien
Puechal, Xavier
Masson, Maeva
Kostine, Marie
Michaut, Alexia
Ramon, Andre
Wendling, Daniel
Costedoat-Chalumeau, Nathalie
Richette, Pascal
Marotte, Hubert
Vix-Portet, Justine
Dubost, Jean-Jacques
Ottaviani, Sebastien
Mouterde, Gael
Grasland, Anne
Frazier, Aline
Germain, Vincent
Coury, Fabienne
Tournadre, Anne
Soubrier, Martin
Cavalie, Laurent
Brevet, Pauline
Zabraniecki, Laurent
Jamard, Benedicte
Couture, Guillaume
Arnaud, Laurent
Richez, Christophe
Degboe, Yannick
Ruyssen-Witrand, Adeline
Constantin, Arnaud
eng
England
2023/12/24
J Infect. 2024 Feb;88(2):132-138. doi: 10.1016/j.jinf.2023.12.010. Epub 2023 Dec 22.). @article{RN2123,
title = {Diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease: Data from the French Tw-IRD registry},
author = {D. Caillet Portillo and X. Puechal and M. Masson and M. Kostine and A. Michaut and A. Ramon and D. Wendling and N. Costedoat-Chalumeau and P. Richette and H. Marotte and J. Vix-Portet and J. J. Dubost and S. Ottaviani and G. Mouterde and A. Grasland and A. Frazier and V. Germain and F. Coury and A. Tournadre and M. Soubrier and L. Cavalie and P. Brevet and L. Zabraniecki and B. Jamard and G. Couture and L. Arnaud and C. Richez and Y. Degboe and A. Ruyssen-Witrand and A. Constantin},
url = {https://www.ncbi.nlm.nih.gov/pubmed/38141787},
doi = {10.1016/j.jinf.2023.12.010},
issn = {1532-2742 (Electronic) 0163-4453 (Linking)},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {J Infect},
volume = {88},
number = {2},
pages = {132-138},
abstract = {OBJECTIVES: Tropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease-modifying antirheumatic drugs. We investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease. METHODS: We initiated a registry including patients with disease-modifying antirheumatic drugs-treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease. RESULTS: Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases. CONCLUSIONS: Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation.},
note = {Caillet Portillo, Damien
Puechal, Xavier
Masson, Maeva
Kostine, Marie
Michaut, Alexia
Ramon, Andre
Wendling, Daniel
Costedoat-Chalumeau, Nathalie
Richette, Pascal
Marotte, Hubert
Vix-Portet, Justine
Dubost, Jean-Jacques
Ottaviani, Sebastien
Mouterde, Gael
Grasland, Anne
Frazier, Aline
Germain, Vincent
Coury, Fabienne
Tournadre, Anne
Soubrier, Martin
Cavalie, Laurent
Brevet, Pauline
Zabraniecki, Laurent
Jamard, Benedicte
Couture, Guillaume
Arnaud, Laurent
Richez, Christophe
Degboe, Yannick
Ruyssen-Witrand, Adeline
Constantin, Arnaud
eng
England
2023/12/24
J Infect. 2024 Feb;88(2):132-138. doi: 10.1016/j.jinf.2023.12.010. Epub 2023 Dec 22.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: Tropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease-modifying antirheumatic drugs. We investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease. METHODS: We initiated a registry including patients with disease-modifying antirheumatic drugs-treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease. RESULTS: Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases. CONCLUSIONS: Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation. |
Salles, Juliette; Eddiry, Sanaa; Amri, Saber; Galindo, Mélissa; Lacassagne, Emmanuelle; George, Simon; Mialhe, Xavier; Lhuillier, Émeline; Franchitto, Nicolas; Jeanneteau, Freddy; Gennero, Isabelle; Salles, Jean Pierre; Tauber, Maithé Differential DNA methylation in iPSC-derived dopaminergic neurons: a step forward on the role of SNORD116 microdeletion in the pathophysiology of addictive behavior in Prader-Willi syndrome Journal Article In: Molecular Psychiatry, no. March, 2024, ISSN: 14765578. @article{Salles2024,
title = {Differential DNA methylation in iPSC-derived dopaminergic neurons: a step forward on the role of SNORD116 microdeletion in the pathophysiology of addictive behavior in Prader-Willi syndrome},
author = {Juliette Salles and Sanaa Eddiry and Saber Amri and Mélissa Galindo and Emmanuelle Lacassagne and Simon George and Xavier Mialhe and Émeline Lhuillier and Nicolas Franchitto and Freddy Jeanneteau and Isabelle Gennero and Jean Pierre Salles and Maithé Tauber},
doi = {10.1038/s41380-024-02542-4},
issn = {14765578},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Molecular Psychiatry},
number = {March},
publisher = {Springer US},
abstract = {Introduction: A microdeletion including the SNORD116 gene (SNORD116 MD) has been shown to drive the Prader-Willi syndrome (PWS) features. PWS is a neurodevelopmental disorder clinically characterized by endocrine impairment, intellectual disability and psychiatric symptoms such as a lack of emotional regulation, impulsivity, and intense temper tantrums with outbursts. In addition, this syndrome is associated with a nutritional trajectory characterized by addiction-like behavior around food in adulthood. PWS is related to the genetic loss of expression of a minimal region that plays a potential role in epigenetic regulation. Nevertheless, the role of the SNORD116 MD in DNA methylation, as well as the impact of the oxytocin (OXT) on it, have never been investigated in human neurons. Methods: We studied the methylation marks in induced pluripotent stem-derived dopaminergic neurons carrying a SNORD116 MD in comparison with those from an age-matched adult healthy control. We also performed identical neuron differentiation in the presence of OXT. We performed a genome-wide DNA methylation analysis from the iPSC-derived dopaminergic neurons by reduced-representation bisulfite sequencing. In addition, we performed RNA sequencing analysis in these iPSC-derived dopaminergic neurons differentiated with or without OXT. Results: The analysis revealed that 153,826 cytosines were differentially methylated between SNORD116 MD neurons and control neurons. Among the differentially methylated genes, we determined a list of genes also differentially expressed. Enrichment analysis of this list encompassed the dopaminergic system with COMT and SLC6A3. COMT displayed hypermethylation and under-expression in SNORD116 MD, and SLC6A3 displayed hypomethylation and over-expression in SNORD116 MD. RT-qPCR confirmed significant over-expression of SLC6A3 in SNORD116 MD neurons. Moreover, the expression of this gene was significantly decreased in the case of OXT adjunction during the differentiation. Conclusion: SNORD116 MD dopaminergic neurons displayed differential methylation and expression in the COMT and SLC6A3 genes, which are related to dopaminergic clearance.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction: A microdeletion including the SNORD116 gene (SNORD116 MD) has been shown to drive the Prader-Willi syndrome (PWS) features. PWS is a neurodevelopmental disorder clinically characterized by endocrine impairment, intellectual disability and psychiatric symptoms such as a lack of emotional regulation, impulsivity, and intense temper tantrums with outbursts. In addition, this syndrome is associated with a nutritional trajectory characterized by addiction-like behavior around food in adulthood. PWS is related to the genetic loss of expression of a minimal region that plays a potential role in epigenetic regulation. Nevertheless, the role of the SNORD116 MD in DNA methylation, as well as the impact of the oxytocin (OXT) on it, have never been investigated in human neurons. Methods: We studied the methylation marks in induced pluripotent stem-derived dopaminergic neurons carrying a SNORD116 MD in comparison with those from an age-matched adult healthy control. We also performed identical neuron differentiation in the presence of OXT. We performed a genome-wide DNA methylation analysis from the iPSC-derived dopaminergic neurons by reduced-representation bisulfite sequencing. In addition, we performed RNA sequencing analysis in these iPSC-derived dopaminergic neurons differentiated with or without OXT. Results: The analysis revealed that 153,826 cytosines were differentially methylated between SNORD116 MD neurons and control neurons. Among the differentially methylated genes, we determined a list of genes also differentially expressed. Enrichment analysis of this list encompassed the dopaminergic system with COMT and SLC6A3. COMT displayed hypermethylation and under-expression in SNORD116 MD, and SLC6A3 displayed hypomethylation and over-expression in SNORD116 MD. RT-qPCR confirmed significant over-expression of SLC6A3 in SNORD116 MD neurons. Moreover, the expression of this gene was significantly decreased in the case of OXT adjunction during the differentiation. Conclusion: SNORD116 MD dopaminergic neurons displayed differential methylation and expression in the COMT and SLC6A3 genes, which are related to dopaminergic clearance. |
