@article{RN2124,

title = {Characteristics of the (Auto)Reactive T Cells in Rheumatoid Arthritis According to the Immune Epitope Database},

author = {C. Carle and Y. Degboe and A. Ruyssen-Witrand and M. I. Arleevskaya and C. Clavel and Y. Renaudineau},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36901730},

doi = {10.3390/ijms24054296},

issn = {1422-0067 (Electronic) 1422-0067 (Linking)},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Int J Mol Sci},

volume = {24},

number = {5},

abstract = {T cells are known to be involved in the pathogenesis of rheumatoid arthritis (RA). Accordingly, and to better understand T cells' contribution to RA, a comprehensive review based on an analysis of the Immune Epitope Database (IEDB) was conducted. An immune CD8+ T cell senescence response is reported in RA and inflammatory diseases, which is driven by active viral antigens from latent viruses and cryptic self-apoptotic peptides. RA-associated pro-inflammatory CD4+ T cells are selected by MHC class II and immunodominant peptides, which are derived from molecular chaperones, host extra-cellular and cellular peptides that could be post-translationally modified (PTM), and bacterial cross-reactive peptides. A large panel of techniques have been used to characterize (auto)reactive T cells and RA-associated peptides with regards to their interaction with the MHC and TCR, capacity to enter the docking site of the shared epitope (DRB1-SE), capacity to induce T cell proliferation, capacity to select T cell subsets (Th1/Th17, Treg), and clinical contribution. Among docking DRB1-SE peptides, those with PTM expand autoreactive and high-affinity CD4+ memory T cells in RA patients with an active disease. Considering original therapeutic options in RA, mutated, or altered peptide ligands (APL) have been developed and are tested in clinical trials.},

note = {Carle, Caroline 

Degboe, Yannick 

Ruyssen-Witrand, Adeline 

Arleevskaya, Marina I 

Clavel, Cyril 

Renaudineau, Yves 

eng 

2023/Societe Francaise de Rhumatologie/ 

17-15-01099/Russian Science Foundation/ 

Review 

Switzerland 

2023/03/12 

Int J Mol Sci. 2023 Feb 21;24(5):4296. doi: 10.3390/ijms24054296.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37033984,

title = {Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic},

author = {Jérôme de Sèze and Elisabeth Maillart and Antoine Gueguen and David A Laplaud and Laure Michel and Eric Thouvenot and Hélène Zephir and Luc Zimmer and Damien Biotti and Roland Liblau},

doi = {10.3389/fimmu.2023.1004795},

issn = {1664-3224},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Front Immunol},

volume = {14},

pages = {1004795},

abstract = {The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ B and CD20+ T cells and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, and lessen disability progression in patients with relapsing multiple sclerosis. Rituximab, ocrelizumab, and ofatumumab are currently used in clinical practice, while phase III clinical trials for ublituximab have been recently completed. In this review, we compare the four anti-CD20 antibodies in terms of their mechanisms of action, routes of administration, immunological targets, and pharmacokinetic properties. A deeper understanding of the individual properties of these molecules in relation to their efficacy and safety profiles is critical for their use in clinical practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37122721,

title = {Cerebrospinal fluid proteomics in recent-onset Narcolepsy type 1 reveals activation of the complement system},

author = {Ikram Ayoub and Yves Dauvilliers and Lucie Barateau and Thaïs Vermeulen and Emmanuelle Mouton-Barbosa and Marlène Marcellin and Anne Gonzalez-de-Peredo and Catharina C Gross and Abdelhadi Saoudi and Roland Liblau},

doi = {10.3389/fimmu.2023.1108682},

issn = {1664-3224},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Front Immunol},

volume = {14},

pages = {1108682},

abstract = {INTRODUCTION: Narcolepsy type 1 (NT1) is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the orexin neuropeptides in the lateral hypothalamus. Genetic and environmental factors strongly suggest the involvement of the immune system in the loss of orexin neurons. The cerebrospinal fluid (CSF), secreted locally and surrounding the central nervous system (CNS), represents an accessible window into CNS pathological processes.nnMETHODS: To gain insight into the biological and molecular changes in NT1 patients, we performed a comparative proteomics analysis of the CSF from 21 recent-onset NT1 patients and from two control groups: group 1 with somatoform disorders, and group 2 patients with hypersomnia other than NT1, to control for any potential effect of sleep disturbances on CSF composition. To achieve an optimal proteomic coverage analysis, the twelve most abundant CSF proteins were depleted, and samples were analyzed by nano-flow liquid chromatography tandem mass spectrometry (nano-LC-MS/MS) using the latest generation of hybrid Orbitrap mass spectrometer.nnRESULTS AND DISCUSSION: Our study allowed the identification and quantification of up to 1943 proteins, providing a remarkably deep analysis of the CSF proteome. Interestingly, gene set enrichment analysis indicated that the complement and coagulation systems were enriched and significantly activated in NT1 patients in both cohorts analyzed. Notably, the lectin and alternative complement pathway as well as the downstream lytic membrane attack complex were congruently increased in NT1. Our data suggest that the complement dysregulation in NT1 patients can contribute to immunopathology either by directly promoting tissue damage or as part of local inflammatory responses. We therefore reveal an altered composition of the CSF proteome in NT1 patients, which points to an ongoing inflammatory process contributed, at least in part, by the complement system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36865563,

title = {Editorial: Dysregulation of Th17 and Treg cells in autoimmune diseases},

author = {Anne L Astier and David M Kofler},

doi = {10.3389/fimmu.2023.1151836},

issn = {1664-3224},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Front Immunol},

volume = {14},

pages = {1151836},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lacouture_kinetic_2023,

title = {Kinetic measurements of human CD8+ Ŧ cell cytotoxic activity in a 384-well plate format},

author = {Lacouture, Claire and Prunier, Guilhèn and Dupré, Loïc},

doi = {10.1016/bs.mcb.2022.07.014},

issn = {0091-679X},

year  = {2023},

date = {2023-01-01},

journal = {Methods Cell Biol},

volume = {178},

pages = {121--133},

abstract = {The elimination of infected or cancerous cells by CD8+ cytotoxic T lymphocytes (CTL) is a crucial effector mechanism of the immune system. Upon antigen recognition, CTL stop migrating, establish a tight contact with target cells and deliver cytotoxic molecules such as perforin and granzymes that lead to target cell apoptosis. The ability of CTL to control a population of infected cells or a tumor depends on multiple parameters, such as the relative numbers of CTL and target cells, the intrinsic cytotoxic activity of CTL, the intrinsic resistance of target cells and the repertoire of immune checkpoints tuning cytotoxic activity at the CTL:target cell interface. In this context, in vitro assays to precisely measure CTL:target cell interactions and cytotoxic activity over time are required to monitor natural or therapeutic responses. We here present an image-based method that allows recording of positions and survival of CTL and target cells over time in a high-throughput format. The protocol relies on the staining of CTL and target cells with fluorescent dyes and the automated imaging of cells deposited in wells of a 384-well plate with an automated cell imaging device. We discuss potential applications offered by the kinetic assessment of CTL cytotoxic activity in a high-throughput format.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{prunier_metrics_2023,

title = {Metrics of 2D immunological synapses in human Ŧ cells via high-content confocal cell imaging},

author = {Prunier, Guilhèn and Chaves, Beatriz and Lacouture, Claire and Dupré, Loïc},

doi = {10.1016/bs.mcb.2022.07.013},

issn = {0091-679X},

year  = {2023},

date = {2023-01-01},

journal = {Methods Cell Biol},

volume = {178},

pages = {107--120},

abstract = {Immunological synapses (IS) are the privileged site of complex information transfer between T cells and antigen presenting cells. IS are highly structured in terms of actin and tubulin cytoskeleton organization, receptor and proximal signal patterning, and intracellular organelle polarization. The magnitude and quality of T cell responses upon antigen recognition is dependent on IS molecular organization. For that reason, methods to precisely assess IS parameters are crucial to monitor T cell activation and function in health and disease, but also for T cell centered therapeutic intervention. Confocal and super-resolution microscopy approaches have allowed to characterize the complex structure of the T cell IS. However, those approaches suffer from a low-throughput and low-content format precluding multi-parametric classification of IS across large numbers of samples or stimulatory conditions. Here, we present a protocol of high-content confocal cell imaging in a 384-well plate format adapted to the unbiased analysis of primary T cells forming IS over pre-coated stimulatory molecules. The protocol focuses on the staining of F-actin, pericentrin and granzyme B in CD8+ T cells, but is transposable to other IS molecular markers and lymphocyte subsets. We discuss potential applications offered by the multi-parametric characterization of T cell IS in a high-throughput format.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{c,

title = {Evolution and spread of Plasmodium falciparum mutations associated with resistance to sulfadoxine-pyrimethamine in central Africa: a cross-sectional study},

author = {Guemas, E. and Coppee, R. and Menard, S. and du Manoir, M. and Nsango, S. and Makaba Mvumbi, D. and Nakoune, E. and Eboumbou Moukoko, C. E. and Bouyou Akotet, M. K. and Mirabeau, T. Y. and Manguin, S. and Malekita Yobi, D. and Akiana, J. and Kouna, L. C. and Mawili Mboumba, D. P. and Voumbo-Matoumona, D. F. and Otam, A. L. and Rubbo, P. A. and Lombart, J. P. and Kwanai, E. and Cohen, O. and Iriart, X. and Ayong, L. and Lekana-Douki, J. B. and Ariey, F. and Berry, A.},

year  = {2023},

date = {2023-01-01},

journal = {Lancet Microbe},

abstract = {BACKGROUND: Efficacy of sulfadoxine-pyrimethamine, the malaria chemoprophylaxis used in pregnant women, and in children when combined with amodiaquine, is threatened by the accumulation of mutations in the Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes. Data on the prevalence of resistant alleles in central Africa and the new pfdhps I431V mutation, particularly associated with other mutations to form the pfdhps vagKgs allele, are scarce. We explored the frequency and geographical distribution of pfdhps and pfdhfr mutations in central Africa in 2014-18, and assessed the evolutionary origin of the vagKgs allele. METHODS: Samples were collected at 18 health-care centres in seven countries (Angola, Cameroon, Central African Republic, Democratic Republic of the Congo, Gabon, Nigeria, and Republic of the Congo) from patients who showed possible symptoms of malaria between March 1, 2014, and Oct 31, 2018. Samples that were positive for P falciparum were transported to a laboratory in Toulouse, France, and genotyped. The frequency of pfdhfr and pfdhps mutations was studied in 1749 samples. Microsatellites in pfdhps flanking regions and whole-genome analysis compared with parasite genomes from the data-sharing network MalariaGEN were performed on samples carrying the vagKgs allele. FINDINGS: Mapping of the prevalence of single nucleotide polymorphisms and corresponding alleles of pfdhfr and pfdhps showed a substantial spread of alleles associated with sulfadoxine-pyrimethamine resistance in central Africa during the 2014-18 period, especially an increase going west to east in pfdhps alleles carrying the K540E and A581G mutations. A high prevalence of the pfdhps I431V mutation was observed in Cameroon (exceeding 50% in the northern region) and Nigeria. Genomic analysis showed a recent African emergence and a clonal expansion of the most frequent pfdhps vagKgs allele. INTERPRETATION: Reduced sulfadoxine-pyrimethamine efficacy due to increased resistance is a worrying situation, especially because the malaria transmission level is high in central Africa. Although the resistance phenotype remains to be confirmed, the emergence and spread of the vagKgs allele in west and central Africa could challenge the use of sulfadoxine-pyrimethamine. FUNDING: Toulouse Institute for Infectious and Inflammatory Diseases.},

note = {doi: 10.1016/S2666-5247(23)00211-2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{c,

title = {Effect of sulfadoxine-pyrimethamine chemoprophylaxis in pregnant women on selection of the new P. falciparum dhps quintuple mutant carrying the I431V mutation},

author = {Cohen, O. and Guemas, E. and Menard, S. and Tsague Kenfack, M. and Talom Ngassa, C. and Iriart, X. and Bidzogo Lebobo, M. and Ondobo Ekae, C. and Eboumbou, C. and Tiyou Kenmeni, C. and Berry, A.},

year  = {2023},

date = {2023-01-01},

journal = {J Antimicrob Chemother},

volume = {78},

number = {3},

pages = {665-668},

abstract = {BACKGROUND: A new mutation in the Plasmodium falciparum dihydropteroate synthetase gene (pfdhps), I431V, has been identified in several countries of Central and West Africa. This mutation is mostly found in association with four other SNPs on pfdhps (S436A, A437G, A581G and A613S), forming a quintuple mutant (vagKgs) and almost always associated with the Plasmodium falciparum dihydrofolate reductase gene (pfdhfr) CirnI (C50R, N51I, S108N) triple mutant. To date, nothing is known about the impact of this new pfdhps genotype on sulfadoxine-pyrimethamine (SP) resistance. OBJECTIVES: We sought to assess the prevalence of this pfdhps vagKgs quintuple mutant in two groups of pregnant women with malaria, one that took intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and one that did not. METHODS: The pfdhfr and pfdhps genes from Plasmodium falciparum isolates collected in Yaounde (Cameroon) from pregnant women with symptomatic malaria under IPTp-SP or not, were sequenced. RESULTS: Of 159 patients evaluated, 70 had already taken SP during pregnancy and 89 had never taken SP. Only the vagKgs allele was significantly overrepresented in the SP+ group (21.4% versus 3.4%; P < 0.001), whereas the ISgKAA mutant, widely distributed in this area and known to be less susceptible to SP, tended to be less abundant in this group (48.6% versus 64.0%; P = 0.0503). CONCLUSIONS: We found a strong overrepresentation of the CirnI/vagKgs haplotype in the IPTp-SP pregnant group, suggesting a high level of resistance of this mutant to SP. This could compromise not only the effectiveness of IPTp-SP but also the seasonal malaria chemoprevention of young children, now widely implemented.},

note = { doi: 10.1093/jac/dkac432.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN4495,

title = {The pressing need for a global HEV vaccine},

author = {Peron, J. M. and Larrue, H. and Izopet, J. and Buti, M.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37003442},

doi = {10.1016/j.jhep.2023.03.024},

issn = {1600-0641 (Electronic) 

0168-8278 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {J Hepatol},

volume = {79},

number = {3},

pages = {876-880},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2418,

title = {TLR8 escapes X chromosome inactivation in human monocytes and CD4(+) T cells},

author = {Youness, A. and Cenac, C. and Faz-Lopez, B. and Grunenwald, S. and Barrat, F. J. and Chaumeil, J. and Mejia, J. E. and Guery, J. C.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37723501},

doi = {10.1186/s13293-023-00544-5},

issn = {2042-6410 (Electronic) 

2042-6410 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Biol Sex Differ},

volume = {14},

number = {1},

pages = {60},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2417,

title = {Immunological and translational key challenges in systemic lupus erythematosus: A symposium update},

author = {Renaudineau, Y. and Muller, S. and Hedrich, C. M. and Chauveau, D. and Belliere, J. and De Almeida, S. and Damoiseaux, J. and Scherlinger, M. and Guery, J. C. and Sailler, L. and Bost, C.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37065621},

doi = {10.1016/j.jtauto.2023.100199},

issn = {2589-9090 (Electronic) 

2589-9090 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {J Transl Autoimmun},

volume = {6},

pages = {100199},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2416,

title = {Influence of X chromosome in sex-biased autoimmune diseases},

author = {Miquel, C. H. and Faz-Lopez, B. and Guery, J. C.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36641351},

doi = {10.1016/j.jaut.2023.102992},

issn = {1095-9157 (Electronic) 

0896-8411 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {J Autoimmun},

volume = {137},

pages = {102992},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2415,

title = {B cell-intrinsic TLR7 signaling is required for neutralizing antibody responses to SARS-CoV-2 and pathogen-like COVID-19 vaccines},

author = {Miquel, C. H. and Abbas, F. and Cenac, C. and Foret-Lucas, C. and Guo, C. and Ducatez, M. and Joly, E. and Hou, B. and Guery, J. C.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37438976},

doi = {10.1002/eji.202350437},

issn = {1521-4141 (Electronic) 

0014-2980 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Eur J Immunol},

pages = {e2350437},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2414,

title = {PKCalpha interacts with Ca(v) 1.3 calcium channels to promote the Ca(v) 1.2/Ca(v) 1.3 duo tuning Th2 functions},

author = {Giang, N. and Villeneuve, T. and Maire, K. and Mejia, J. E. and Guery, J. C. and Pelletier, L. and Savignac, M.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36478369},

doi = {10.1111/all.15611},

issn = {1398-9995 (Electronic) 

0105-4538 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Allergy},

volume = {78},

number = {3},

pages = {879-882},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2413,

title = {The Influence of Sex Hormones and X Chromosome in Immune Responses},

author = {Anesi, N. and Miquel, C. H. and Laffont, S. and Guery, J. C.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37695424},

doi = {10.1007/978-3-031-35139-6_2},

issn = {0070-217X (Print) 

0070-217X (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Curr Top Microbiol Immunol},

volume = {441},

pages = {21-59},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{c,

title = {The apicoplast is important for the viability and persistence of Toxoplasma gondii bradyzoites},

author = {Sanchez, S. G. and Bassot, E. and Cerutti, A. and Mai Nguyen, H. and Aida, A. and Blanchard, N. and Besteiro, S.},

year  = {2023},

date = {2023-01-01},

journal = {Proc Natl Acad Sci U S A},

volume = {120},

number = {34},

pages = {e2309043120},

abstract = {Toxoplasma gondii is responsible for toxoplasmosis, a disease that can be serious when contracted during pregnancy, but can also be a threat for immunocompromised individuals. Acute infection is associated with the tachyzoite form that spreads rapidly within the host. However, under stress conditions, some parasites can differentiate into cyst-forming bradyzoites, residing mainly in the central nervous system, retina and muscle. Because this latent form of the parasite is resistant to all currently available treatments, and is central to persistence and transmission of the parasite, specific therapeutic strategies targeting this developmental stage need to be found. T. gondii contains a plastid of endosymbiotic origin called the apicoplast, which is an appealing drug target because it is essential for tachyzoite viability and contains several key metabolic pathways that are largely absent from the mammalian host. Its function in bradyzoites, however, is unknown. Our objective was thus to study the contribution of the apicoplast to the viability and persistence of bradyzoites during chronic toxoplasmosis. We have used complementary strategies based on stage-specific promoters to generate conditional bradyzoite mutants of essential apicoplast genes. Our results show that specifically targeting the apicoplast in both in vitro or in vivo-differentiated bradyzoites leads to a loss of long-term bradyzoite viability, highlighting the importance of this organelle for this developmental stage. This validates the apicoplast as a potential area to look for therapeutic targets in bradyzoites, with the aim to interfere with this currently incurable parasite stage.},

note = {doi:10.1073/pnas.2309043120},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{dupre_deciphering_2023,

title = {Deciphering actin remodelling in immune cells through the prism of actin-related inborn errors of immunity},

author = {Dupré, Loïc and Prunier, Guilhèn},

doi = {10.1016/j.ejcb.2022.151283},

issn = {1618-1298},

year  = {2023},

date = {2023-01-01},

journal = {Eur J Cell Biol},

volume = {102},

number = {1},

pages = {151283},

abstract = {Actin cytoskeleton remodelling drives cell motility, cell to cell contacts, as well as membrane and organelle dynamics. Those cellular activities operate at a particularly high pace in immune cells since these cells migrate through various tissues, interact with multiple cellular partners, ingest microorganisms and secrete effector molecules. The central and multifaceted role of actin cytoskeleton remodelling in sustaining immune cell tasks in humans is highlighted by rare inborn errors of immunity due to mutations in genes encoding proximal and distal actin regulators. In line with the specificity of some of the actin-based processes at work in immune cells, the expression of some of the affected genes, such as WAS, ARPC1B and HEM1 is restricted to the hematopoietic compartment. Exploration of these natural deficiencies highlights the fact that the molecular control of actin remodelling is tuned distinctly in the various subsets of myeloid and lymphoid immune cells and sustains different networks associated with a vast array of specialized tasks. Furthermore, defects in individual actin remodelling proteins are usually associated with partial cellular impairments highlighting the plasticity of actin cytoskeleton remodelling. This review covers the roles of disease-associated actin regulators in promoting the actin-based processes of immune cells. It focuses on the specific molecular function of those regulators across various immune cell subsets and in response to different stimuli. Given the fact that numerous immune-related actin defects have only been characterized recently, we further discuss the challenges lying ahead to decipher the underlying patho-mechanisms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kostel_bal_biallelic_2023,

title = {Biallelic NFATC1 mutations cause an inborn error of immunity with impaired CD8+ Ŧ-cell function and perturbed glycolysis},

author = {Kostel Bal, Sevgi and Giuliani, Sarah and Block, Jana and Repiscak, Peter and Hafemeister, Christoph and Shahin, Tala and Kasap, Nurhan and Ransmayr, Bernhard and Miao, Yirun and van de Wetering, Cheryl and Frohne, Alexandra and Jimenez-Heredia, Raul and Schuster, Michael K. and Zoghi, Samaneh and Hertlein, Vanessa and Thian, Marini and Bykov, Aleksandr and Babayeva, Royala and Bilgic Eltan, Sevgi and Karakoc-Aydiner, Elif and Shaw, Lisa E. and Chowdhury, Iftekhar and Varjosalo, Markku and Argüello, Rafael Jose and Farlik, Matthias and Ozen, Ahmet and Serfling, Edgar Albert Ernst and Dupré, Loïc and Bock, Christoph and Halbritter, Florian and Hannich, J. Thomas and Castanon, Irinka and Kraakman, Michael J. and Baris, Safa and Boztug, Kaan},

doi = {10.1182/blood.2022018303},

issn = {1528-0020},

year  = {2023},

date = {2023-01-01},

journal = {Blood},

pages = {blood.2022018303},

abstract = {The NFAT family of transcription factors plays central roles in adaptive immunity in murine models, however, their contribution to human immune homeostasis remains poorly defined. In a multigenerational pedigree, we identified three patients carrying germline biallelic missense variants in NFATC1, presenting with recurrent infections, hypogammaglobulinemia and decreased antibody responses. The compound heterozygous NFATC1 variants identified in the patients caused decreased stability and reduced binding of DNA and interacting proteins. We observed defects in early activation and proliferation of T and B cells from these patients, amenable to reconstitution upon genetic rescue. Following stimulation, T-cell activation and proliferation were impaired, reaching that of healthy controls with delay indicative of an adaptive capacity of the cells. Assessment of the metabolic capacity of patient T cells, revealed that NFATc1-dysfunction rendered T cells unable to engage in glycolysis following stimulation, although oxidative metabolic processes were intact. We hypothesized that NFATc1-mutant T cells could compensate for the energy deficit due to defective glycolysis by enhanced lipid metabolism as an adaptation, leading to a delayed, but not lost activation responses. Indeed, we observed increased 13C-labelled palmitate incorporation into citrate indicating higher fatty acid oxidation and we demonstrated that metformin and rosiglitazone improved patient T-cell effector functions. Collectively, enabled by our molecular dissection of NFATC1 mutations and extending the role of NFATc1 in human immunity beyond receptor signaling, and reveal evidence of metabolic plasticity in the context of impaired glycolysis observed in patient T cells to remedy delayed effector responses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Martin2022,

title = {Placental extracellular vesicles in maternal-fetal communication during pregnancy},

author = {Charlène Martin and Mathilde Bergamelli and Cécile E. Malnou and Gisela D'Angelo},

doi = {10.1042/bst20220734},

issn = {1470-8752},

year  = {2022},

date = {2022-12-16},

urldate = {2022-12-16},

journal = {Biochem Soc Trans},

volume = {50},

number = {6},

pages = {1785--1795},

publisher = {Portland Press Ltd.},

abstract = {<jats:p>For several years, a growing number of studies have highlighted the pivotal role of placental extracellular vesicles (EVs) throughout pregnancy. These membrane nanovesicles, heterogeneous in nature, composition and origin, are secreted by several trophoblastic cell types and are found in both the maternal and fetal compartments. They can be uptaken by recipient cells and drive a wide variety of physiological and pathological processes. In this review, we provide an overview of the different described roles of placental EVs in various aspects of normal pregnancy, from placenta establishment to maternal immune tolerance towards the fetus and protection against viral infections. In the second part, we present selected examples of pathological pregnancies in which placental EVs are involved, such as gestational diabetes mellitus, pre-eclampsia, and congenital infections. Since the abundance and/or composition of placental EVs is deregulated in maternal serum during pathological pregnancies, this makes them interesting candidates as non-invasive biomarkers for gestational diseases and opens a wide field of translational perspectives.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Matheson2022,

title = {Multiomics analysis couples mRNA turnover and translational control of glutamine metabolism to the differentiation of the activated CD4+ T cell},

author = {Matheson, Louise S. 

and Petkau, Georg 

and S{'a}enz-Narciso, Beatriz 

and D'Angeli, Vanessa 

and McHugh, Jessica 

and Newman, Rebecca 

and Munford, Haydn 

and West, James 

and Chakraborty, Krishnendu 

and Roberts, Jennie 

and {Ł}ukasiak, Sebastian 

and D{'i}az-Mu{ñ}oz, Manuel D. 

and Bell, Sarah E. 

and Dimeloe, Sarah 

and Turner, Martin},

url = {https://doi.org/10.1038/s41598-022-24132-6},

doi = {10.1038/s41598-022-24132-6},

issn = {2045-2322},

year  = {2022},

date = {2022-11-16},

journal = {Scientific Reports},

volume = {12},

number = {1},

pages = {19657},

abstract = {The ZFP36 family of RNA-binding proteins acts post-transcriptionally to repress translation and promote RNA decay. Studies of genes and pathways regulated by the ZFP36 family in CD4+ T cells have focussed largely on cytokines, but their impact on metabolic reprogramming and differentiation is unclear. Using CD4+ T cells lacking Zfp36 and Zfp36l1, we combined the quantification of mRNA transcription, stability, abundance and translation with crosslinking immunoprecipitation and metabolic profiling to determine how they regulate T cell metabolism and differentiation. Our results suggest that ZFP36 and ZFP36L1 act directly to limit the expression of genes driving anabolic processes by two distinct routes: by targeting transcription factors and by targeting transcripts encoding rate-limiting enzymes. These enzymes span numerous metabolic pathways including glycolysis, one-carbon metabolism and glutaminolysis. Direct binding and repression of transcripts encoding glutamine transporter SLC38A2 correlated with increased cellular glutamine content in ZFP36/ZFP36L1-deficient T cells. Increased conversion of glutamine to $alpha$-ketoglutarate in these cells was consistent with direct binding of ZFP36/ZFP36L1 to Gls (encoding glutaminase) and Glud1 (encoding glutamate dehydrogenase). We propose that ZFP36 and ZFP36L1 as well as glutamine and $alpha$-ketoglutarate are limiting factors for the acquisition of the cytotoxic CD4+ T cell fate. Our data implicate ZFP36 and ZFP36L1 in limiting glutamine anaplerosis and differentiation of activated CD4+ T cells, likely mediated by direct binding to transcripts of critical genes that drive these processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}