Publications
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, 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. |
Lacouture, Claire; Chaves, Beatriz; Guipouy, Delphine; Houmadi, Raïssa; Duplan-Eche, Valérie; Allart, Sophie; Destainville, Nicolas; Dupré, Loïc LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity Journal Article In: Nature Communications, vol. 15, no. 1, pp. 407, 2024, ISSN: 2041-1723, (Number: 1 Publisher: Nature Publishing Group). @article{lacouture_lfa-1_2024, T-cell cytotoxic function relies on the cooperation between the highly specific but poorly adhesive T-cell receptor (TCR) and the integrin LFA-1. How LFA-1-mediated adhesion may scale with TCR stimulation strength is ill-defined. Here, we show that LFA-1 conformation activation scales with TCR stimulation to calibrate human T-cell cytotoxicity. Super-resolution microscopy analysis reveals that >1000 LFA-1 nanoclusters provide a discretized platform at the immunological synapse to translate TCR engagement and density of the LFA-1 ligand ICAM-1 into graded adhesion. Indeed, the number of high-affinity conformation LFA-1 nanoclusters increases as a function of TCR triggering strength. Blockade of LFA-1 conformational activation impairs adhesion to target cells and killing. However, it occurs at a lower TCR stimulation threshold than lytic granule exocytosis implying that it licenses, rather than directly controls, the killing decision. We conclude that the organization of LFA-1 into nanoclusters provides a calibrated system to adjust T-cell killing to the antigen stimulation strength. |
Malnou, Cécile E.; Ligat, Gaëtan Editorial: Recent highlights in the development of therapeutic antiviral strategies Journal Article In: Front. Microbiol., vol. 14, 2023, ISSN: 1664-302X. @article{Malnou2023, |
Guilleminault, Laurent; Villeneuve, Thomas; Didier, Alain; Reber, Laurent L; Sigfried, Aurore; Serrano, Elie; de Bonnecaze, Guillaume 2023, ISSN: 1398-9995. @misc{pmid37650422, |
Scholaert, Manon; Peries, Mathias; Braun, Emilie; Martin, Jeremy; Serhan, Nadine; Loste, Alexia; Bruner, Audrey; Basso, Lilian; Chaput, Benoit; Merle, Eric; Descargues, Pascal; Pages, Emeline; Gaudenzio, Nicolas In: bioRxiv, 2023. @article{Scholaert2023, |
Croote, Derek; Wong, Joyce J W; Pecalvel, Cyprien; Leveque, Edouard; Casanovas, Natacha; Kamphuis, Jasper B J; Creeks, Paige; Romero, Johanna; Sohail, Saba; Bedinger, Daniel; Nadeau, Kari C; Chinthrajah, Rebecca S; Reber, Laurent L; Lowman, Henry B Widespread monoclonal IgE antibody convergence to an immunodominant, proanaphylactic Ara h 2 epitope in peanut allergy Journal Article In: J Allergy Clin Immunol, 2023, ISSN: 1097-6825. @article{pmid37748654, BACKGROUND: Despite their central role in peanut allergy, human monoclonal IgE antibodies have eluded characterization.nnOBJECTIVE: We sought to define the sequences, affinities, clonality, and functional properties of human monoclonal IgE antibodies in peanut allergy.nnMETHODS: We applied our single-cell RNA sequencing-based SEQ SIFTER discovery platform to samples from allergic individuals who varied by age, sex, ethnicity, and geographic location in order to understand commonalities in the human IgE response to peanut allergens. Select antibodies were then recombinantly expressed and characterized for their allergen and epitope specificity, affinity, and functional properties.nnRESULTS: We found striking convergent evolution of IgE monoclonal antibodies (mAbs) from several clonal families comprising both memory B cells and plasmablasts. These antibodies bound with subnanomolar affinity to the immunodominant peanut allergen Ara h 2, specifically a linear, repetitive motif. Further characterization of these mAbs revealed their ability to single-handedly cause affinity-dependent degranulation of human mast cells and systemic anaphylaxis on peanut allergen challenge in humanized mice. Finally, we demonstrated that these mAbs, reengineered as IgGs, inhibit significant, but variable, amounts of Ara h 2- and peanut-mediated degranulation of mast cells sensitized with allergic plasma.nnCONCLUSIONS: Convergent evolution of IgE mAbs in peanut allergy is a common phenomenon that can reveal immunodominant epitopes on major allergenic proteins. Understanding the functional properties of these molecules is key to developing therapeutics, such as competitive IgG inhibitors, that are able to stoichiometrically outcompete endogenous IgE for allergen and thereby prevent allergic cascade in cases of accidental allergen exposure. |
Rao, Snigdha N; Zahm, Margot; Casemayou, Audrey; Buleon, Marie; Faguer, Stanislas; Feuillet, Guylène; Iacovoni, Jason S; Joffre, Olivier P; Gonzalez-Fuentes, Ignacio; Lhuillier, Emeline; Martins, Frédéric; Riant, Elodie; Zakaroff-Girard, Alexia; Schanstra, Joost P; Blache, Jean Sébastien Saulnier; Belliere, Julie Single-cell RNA sequencing identifies senescence as therapeutic target in rhabdomyolysis-induced acute kidney injury Journal Article In: Nephrol Dial Transplant, 2023, ISSN: 1460-2385. @article{pmid37697719, BACKGROUND: The role of macrophages in the development of rhabdomyolysis induced acute kidney injury (RM-AKI) has been established, but an in-depth understanding of the changes in the immune landscape could help to improve targeted strategies. Whereas senescence is usually associated with chronic kidney processes, we also wished to explore whether senescence could also occur in AKI and whether senolytics could act on immune cells.nnMETHODS: Single-cell RNA sequencing was used in the murine glycerol-induced RM-AKI model to dissect the transcriptomic characteristics of CD45+ live cells sorted from kidneys 2 days after injury. Public datasets from murine AKI models were reanalyzed to explore cellular senescence signature in tubular epithelial cells (TECs). A combination of senolytics (dasatinib and quercetin, DQ) was administered to mice exposed or not to RM-AKI.nnRESULTS: Unsupervised clustering of nearly 17,000 single-cell transcriptomes identified 7 known immune cell clusters. Sub-clustering of the mononuclear phagocyte cells (MPC), revealed 9 distinct cell sub-populations differently modified with RM. One macrophage cluster was particularly interesting since it behaved as a critical node in a trajectory connecting one MCHIIhigh cluster only present in control to 2 MCHIIlow clusters only present in RM-AKI. This critical cluster expressed a senescence gene signature, that was very different from that of the TECs. Senolytic DQ treatment blocked the switch from a F4/80highCD11blow to F4/80lowCD11bhigh phenotype, which correlated with prolonged nephroprotection in RM-AKI.nnCONCLUSIONS: scRNASeq unmasked novel transitional macrophage subpopulation associated with RM-AKI characterized by the activation of cellular senescence processes. This work provides a proof-of-concept that senolytics nephroprotective effects may rely, at least in part, on subtle immune modulation. |
Martin, Charlène; Ligat, Gaëtan; Malnou, Cécile E. The Yin and the Yang of extracellular vesicles during viral infections Journal Article In: Biomedical Journal, 2023, ISSN: 2319-4170. @article{Martin2023, |
Osma-Garcia, Ines C.; Mouysset, Mailys; Capitan-Sobrino, Dunja; Aubert, Yann; Turner, Martin; Diaz-Muñoz, Manuel D. The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis Journal Article In: Cellular & Molecular Immunology, 2023, ISSN: 2042-0226. @article{Osma-Garcia2023b, Germinal centers (GCs) are essential for the establishment of long-lasting antibody responses. GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome. However, the critical proteins driving these key mechanisms are still unknown. Here, we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses. TIA1- and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection, expansion and differentiation into B-cell clones producing high-affinity antibodies. Mechanistically, TIA1 and TIAL1 control the transcriptional identity of dark- and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1. Thus, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells. |
Tauber#, Marie; Basso#, Lilian; Martin#, Jeremy; Bostan, Luciana; Pinto, Marlene Magalhaes; Thierry, Guilhem R; Houmadi, Raïssa; Serhan, Nadine; Loste, Alexia; Blériot, Camille; Kamphuis, Jasper B J; Grujic, Mirjana; Kjellén, Lena; Pejler, Gunnar; Paul, Carle; Dong, Xinzhong; Galli, Stephen J; Reber, Laurent L; Ginhoux, Florent; Bajenoff, Marc; Gentek, Rebecca; Gaudenzio, Nicolas Landscape of mast cell populations across organs in mice and humans Journal Article In: Journal of Experimental Medicine, 2023. @article{Tauber#2023, |
Gonzalez-Fierro, Carmen; Fonte, Coralie; Dufourd, Eloïse; Cazaentre, Vincent; Aydin, Sidar; Engelhardt, Britta; Caspi, Rachel R; Xu, Biying; Martin-Blondel, Guillaume; Spicer, Julie A; Trapani, Joseph A; Bauer, Jan; Liblau, Roland S; Bost, Chloé Effects of a Small-Molecule Perforin Inhibitor in a Mouse Model of CD8 T Cell-Mediated Neuroinflammation Journal Article In: Neurol Neuroimmunol Neuroinflamm, vol. 10, no. 4, 2023, ISSN: 2332-7812. @article{pmid37080596, BACKGROUND AND OBJECTIVES: Alteration of the blood-brain barrier (BBB) at the interface between blood and CNS parenchyma is prominent in most neuroinflammatory diseases. In several neurologic diseases, including cerebral malaria and Susac syndrome, a CD8 T cell-mediated targeting of endothelial cells of the BBB (BBB-ECs) has been implicated in pathogenesis.nnMETHODS: In this study, we used an experimental mouse model to evaluate the ability of a small-molecule perforin inhibitor to prevent neuroinflammation resulting from cytotoxic CD8 T cell-mediated damage of BBB-ECs.nnRESULTS: Using an in vitro coculture system, we first identified perforin as an essential molecule for killing of BBB-ECs by CD8 T cells. We then found that short-term pharmacologic inhibition of perforin commencing after disease onset restored motor function and inhibited the neuropathology. Perforin inhibition resulted in preserved BBB-EC viability, maintenance of the BBB, and reduced CD8 T-cell accumulation in the brain and retina.nnDISCUSSION: Therefore, perforin-dependent cytotoxicity plays a key role in the death of BBB-ECs inflicted by autoreactive CD8 T cells in a preclinical model and potentially represents a therapeutic target for CD8 T cell-mediated neuroinflammatory diseases, such as cerebral malaria and Susac syndrome. |
Geeraerts, Thomas; Guilbeau-Frugier, Céline; Garcia, Cédric; Memier, Vincent; Raposo, Nicolas; Bonneville, Fabrice; Gales, Céline; Darcourt, Jean; Voisin, Sophie; Ribes, Agnès; Piel-Julian, Marie; Bounes, Fanny; Albucher, Jean François; Roux, Franck-Emmanuel; Izopet, Jacques; Telmon, Norbert; Olivot, Jean Marc; Sié, Pierre; Bauer, Jan; Payrastre, Bernard; Liblau, Roland S Immunohistologic Features of Cerebral Venous Thrombosis Due to Vaccine-Induced Immune Thrombotic Thrombocytopenia Journal Article In: Neurol Neuroimmunol Neuroinflamm, vol. 10, no. 4, 2023, ISSN: 2332-7812. @article{pmid37236806, OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center.nnMETHODS: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination.nnRESULTS: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall.nnDISCUSSION: Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process. |
Liblau, Roland S; Latorre, Daniela; Kornum, Birgitte R; Dauvilliers, Yves; Mignot, Emmanuel J The immunopathogenesis of narcolepsy type 1 Journal Article In: Nat Rev Immunol, 2023, ISSN: 1474-1741. @article{pmid37400646, Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT; also known as orexin) peptides. An immune-mediated pathology for NT1 has long been suspected given its exceptionally tight association with the MHC class II allele HLA-DQB1*06:02, as well as recent genetic evidence showing associations with polymorphisms of T cell receptor genes and other immune-relevant loci and the increased incidence of NT1 that has been observed after vaccination with the influenza vaccine Pandemrix. The search for both self-antigens and foreign antigens recognized by the pathogenic T cell response in NT1 is ongoing. Increased T cell reactivity against HCRT has been consistently reported in patients with NT1, but data demonstrating a primary role for T cells in neuronal destruction are currently lacking. Animal models are providing clues regarding the roles of autoreactive CD4 and CD8 T cells in the disease. Elucidation of the pathogenesis of NT1 will allow for the development of targeted immunotherapies at disease onset and could serve as a model for other immune-mediated neurological diseases. |
Andrea; Carrie Pichler, Nadege; Cuisinier TCR-independent CD137 (4-1BB) signaling promotes CD8+-exhausted T cell proliferation and terminal differentiation Journal Article In: Immunity, vol. 56, pp. 1-18, 2023. @article{Pichler2023, CD137 (4-1BB)-activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by CD137 and its role in cancer immune surveillance remain unresolved. Using T cell-specific deletion and agonist antibodies, we found that CD137 modulates tumor infiltration of CD8+-exhausted T (Tex) cells expressing PD1, Lag-3, and Tim-3 inhibitory receptors. T cell-intrinsic, TCR-independent CD137 signaling stimulated the proliferation and the terminal differentiation of Tex precursor cells through a mechanism involving the RelA and cRel canonical NF-κB subunits and Tox-dependent chromatin remodeling. While Tex cell accumulation induced by prophylactic CD137 agonists favored tumor growth, anti-PD1 efficacy was improved with subsequent CD137 stimulation in pre-clinical mouse models. Better understanding of T cell exhaustion has crucial implications for the treatment of cancer and infectious diseases. Our results identify CD137 as a critical regulator of Tex cell expansion and differentiation that holds potential for broad therapeutic applications. |
Scholaert†, Manon; Houmadi†, Raissa; Martin†, Jeremy; Serhan†, Nadine; Tauber, Marie; Braun, Emilie; Basso, Lilian; Merle, Eric; Descargues, Pascal; Viguier, Manuelle; Lesort, Cécile; Chaput, Benoît; Kanitakis, Jean; Jullien, Denis; Livideanu, Cristina Bulai; Lamant, Laurence; Pagès, Emeline; Gaudenzio, Nicolas 3D deconvolution of human skin immune architecture with Multiplex Annotated Tissue Imaging System Journal Article In: Science Advances, 2023. @article{Scholaert†2023, |
Block, Jana; Rashkova, Christina; Castanon, Irinka; Zoghi, Samaneh; Platon, Jessica; Ardy, Rico C.; Fujiwara, Mitsuhiro; Chaves, Beatriz; Schoppmeyer, Rouven; van der Made, Caspar I.; Jimenez Heredia, Raul; Harms, Frederike L.; Alavi, Samin; Alsina, Laia; Sanchez Moreno, Paula; Ávila Polo, Rainiero; Cabrera-Pérez, Rocío; Kostel Bal, Sevgi; Pfajfer, Laurène; Ransmayr, Bernhard; Mautner, Anna-Katharina; Kondo, Ryohei; Tinnacher, Anna; Caldera, Michael; Schuster, Michael; Domínguez Conde, Cecilia; Platzer, René; Salzer, Elisabeth; Boyer, Thomas; Brunner, Han G.; Nooitgedagt-Frons, Judith E.; Iglesias, Estíbaliz; Deyà-Martinez, Angela; Camacho-Lovillo, Marisol; Menche, Jörg; Bock, Christoph; Huppa, Johannes B.; Pickl, Winfried F.; Distel, Martin; Yoder, Jeffrey A.; Traver, David; Engelhardt, Karin R.; Linden, Tobias; Kager, Leo; Hannich, J. Thomas; Hoischen, Alexander; Hambleton, Sophie; Illsinger, Sabine; Da Costa, Lydie; Kutsche, Kerstin; Chavoshzadeh, Zahra; van Buul, Jaap D.; Antón, Jordi; Calzada-Hernández, Joan; Neth, Olaf; Viaud, Julien; Nishikimi, Akihiko; Dupré, Loïc; Boztug, Kaan Systemic Inflammation and Normocytic Anemia in DOCK11 Deficiency Journal Article In: N Engl J Med, 2023, ISSN: 1533-4406. @article{block_systemic_2023, BACKGROUND: Increasing evidence links genetic defects affecting actin-regulatory proteins to diseases with severe autoimmunity and autoinflammation, yet the underlying molecular mechanisms are poorly understood. Dedicator of cytokinesis 11 (DOCK11) activates the small Rho guanosine triphosphatase (GTPase) cell division cycle 42 (CDC42), a central regulator of actin cytoskeleton dynamics. The role of DOCK11 in human immune-cell function and disease remains unknown. METHODS: We conducted genetic, immunologic, and molecular assays in four patients from four unrelated families who presented with infections, early-onset severe immune dysregulation, normocytic anemia of variable severity associated with anisopoikilocytosis, and developmental delay. Functional assays were performed in patient-derived cells, as well as in mouse and zebrafish models. RESULTS: We identified rare, X-linked germline mutations in DOCK11 in the patients, leading to a loss of protein expression in two patients and impaired CDC42 activation in all four patients. Patient-derived T cells did not form filopodia and showed abnormal migration. In addition, the patient-derived T cells, as well as the T cells from Dock11-knockout mice, showed overt activation and production of proinflammatory cytokines that were associated with an increased degree of nuclear translocation of nuclear factor of activated T cell 1 (NFATc1). Anemia and aberrant erythrocyte morphologic features were recapitulated in a newly generated dock11-knockout zebrafish model, and anemia was amenable to rescue on ectopic expression of constitutively active CDC42. CONCLUSIONS: Germline hemizygous loss-of-function mutations affecting the actin regulator DOCK11 were shown to cause a previously unknown inborn error of hematopoiesis and immunity characterized by severe immune dysregulation and systemic inflammation, recurrent infections, and anemia. (Funded by the European Research Council and others.). |
Defaye, Manon; Iftinca, Mircea C.; Gadotti, Vinicius M.; Basso, Lilian; Abdullah, Nasser S.; Cuménal, Mélissa; Agosti, Francina; Hassan, Ahmed; Flynn, Robyn; Martin, Jérémy; Soubeyre, Vanessa; Poulen, Gaetan; Lonjon, Nicolas; Vachiery-Lahaye, Florence; Bauchet, Luc; Mery, Pierre Francois; Bourinet, Emmanuel; Zamponi, Gerald W.; Altier, Christophe The neuronal tyrosine kinase receptor ligand ALKAL2 mediates persistent pain Journal Article In: The Journal of Clinical Investigation, 2023. @article{Defaye2023, |
Seifinejad, Ali; Ramosaj, Mergim; Shan, Ling; Li, Sha; Possovre, Marie-Laure; Pfister, Corinne; Fronczek, Rolf; Garrett-Sinha, Lee A; Frieser, David; Honda, Makoto; Arribat, Yoan; Grepper, Dogan; Amati, Francesca; Picot, Marie; Agnoletto, Andrea; Iseli, Christian; Chartrel, Nicolas; Liblau, Roland; Lammers, Gert J; Vassalli, Anne; Tafti, Mehdi Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy Journal Article In: Proc Natl Acad Sci U S A, vol. 120, no. 19, pp. e2220911120, 2023, ISSN: 1091-6490. @article{pmid37126681, Narcolepsy with cataplexy is a sleep disorder caused by deficiency in the hypothalamic neuropeptide hypocretin/orexin (HCRT), unanimously believed to result from autoimmune destruction of hypocretin-producing neurons. HCRT deficiency can also occur in secondary forms of narcolepsy and be only temporary, suggesting it can occur without irreversible neuronal loss. The recent discovery that narcolepsy patients also show loss of hypothalamic (corticotropin-releasing hormone) CRH-producing neurons suggests that other mechanisms than cell-specific autoimmune attack, are involved. Here, we identify the HCRT cell-colocalized neuropeptide QRFP as the best marker of HCRT neurons. We show that if HCRT neurons are ablated in mice, in addition to transcript is also lost in the lateral hypothalamus, while in mice where only the gene is inactivated is unchanged. Similarly, postmortem hypothalamic tissues of narcolepsy patients show preserved expression, suggesting the neurons are present but fail to actively produce HCRT. We show that the promoter of the gene of patients exhibits hypermethylation at a methylation-sensitive and evolutionary-conserved PAX5:ETS1 transcription factor-binding site, suggesting the gene is subject to transcriptional silencing. We show also that in addition to HCRT, and Dynorphin () gene promoters, exhibit hypermethylation in the hypothalamus of patients. Altogether, we propose that , , and are epigenetically silenced by a hypothalamic assault (inflammation) in narcolepsy patients, without concurrent cell death. Since methylation is reversible, our findings open the prospect of reversing or curing narcolepsy. |
Aydin, Sidar; Pareja, Javier; Schallenberg, Vivianne M; Klopstein, Armelle; Gruber, Thomas; Page, Nicolas; Bouillet, Elisa; Blanchard, Nicolas; Liblau, Roland; Körbelin, Jakob; Schwaninger, Markus; Johnson, Aaron J; Schenk, Mirjam; Deutsch, Urban; Merkler, Doron; Engelhardt, Britta Antigen recognition detains CD8 T cells at the blood-brain barrier and contributes to its breakdown Journal Article In: Nat Commun, vol. 14, no. 1, pp. 3106, 2023, ISSN: 2041-1723. @article{pmid37253744, Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system (CNS) are early hallmarks of multiple sclerosis (MS). High numbers of CD8 T cells are found in MS lesions, and antigen (Ag) presentation at the BBB has been proposed to promote CD8 T cell entry into the CNS. Here, we show that brain endothelial cells process and cross-present Ag, leading to effector CD8 T cell differentiation. Under physiological flow in vitro, endothelial Ag presentation prevented CD8 T cell crawling and diapedesis resulting in brain endothelial cell apoptosis and BBB breakdown. Brain endothelial Ag presentation in vivo was limited due to Ag uptake by CNS-resident macrophages but still reduced motility of Ag-specific CD8 T cells within CNS microvessels. MHC class I-restricted Ag presentation at the BBB during neuroinflammation thus prohibits CD8 T cell entry into the CNS and triggers CD8 T cell-mediated focal BBB breakdown. |
P, Lifar; F, Montastruc; LL, Reber; JF, Magnaval; L, Guilleminault Parasitic Infections and Biological Therapies Targeting Type 2 Inflammation: A VigiBase Study Journal Article In: 2023. @article{36883943, |
Recent publications
2023 |
Osma-Garcia, Ines C.; Mouysset, Mailys; Capitan-Sobrino, Dunja; Aubert, Yann; Turner, Martin; Diaz-Muñoz, Manuel D. The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis Journal Article In: Cellular & Molecular Immunology, 2023, ISSN: 2042-0226. @article{Osma-Garcia2023b, Germinal centers (GCs) are essential for the establishment of long-lasting antibody responses. GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome. However, the critical proteins driving these key mechanisms are still unknown. Here, we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses. TIA1- and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection, expansion and differentiation into B-cell clones producing high-affinity antibodies. Mechanistically, TIA1 and TIAL1 control the transcriptional identity of dark- and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1. Thus, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells. |
P, Lifar; F, Montastruc; LL, Reber; JF, Magnaval; L, Guilleminault Parasitic Infections and Biological Therapies Targeting Type 2 Inflammation: A VigiBase Study Journal Article In: 2023. @article{36883943, |
E, Lamanna; E, Conde; A, Mougel; J, Bonnefoy; F, Colaone; O, Godon; S, Hamdi; JBJ, Kamphuis; B, Drouet; V, Serra; P, Bruhns; LL, Reber A vaccine targeting human IL-4 and IL-13 protects against asthma in humanized mice. Journal Article In: Allergy, 2023. @article{36799426, |
2022 |
Kamphuis JBJ Worrall WPM, Stackowicz J The anti-FcεRI antibody MAR-1 depletes basophils and cross-reacts with myeloid cells through its Fc portion Journal Article In: Allergy, vol. 77, no. 6, pp. 1903-1906, 2022. @article{WPM2022, |
Gaudenzio N, Liblau RS. Immune cells impede repair of old neurons Journal Article In: Science, vol. 376, no. 6594, pp. 694-695, 2022. @article{N2022, The regenerative capacity of older people is reduced, resulting in decreased tissue function and resilience. Accordingly, the regeneration of the sciatic nerve after injury has been reported to be less efficient and slower in older people (1). One of the hallmarks of aging is altered intercellular communication, which is often accompanied by increased density of immune cells within tissues and excessive release of proinflammatory mediators, called inflammaging (2, 3). In this context, the immune system disturbs tissue homeostasis and impedes functional recovery. However, the precise mechanisms underlying this pathophysiological process are largely elusive, which is a barrier to rational treatment design. On page 715 of this issue, Zhou et al. (4) describe a mechanism by which aged sensory neurons release the chemoattractive protein C-X-C motif chemokine ligand 13 (CXCL13). Upon sciatic nerve injury in aged, but not young, mice, this results in the recruitment of CD8+ T cells that prevent axonal regeneration. |
Congy-Jolivet, N.; Cenac, C.; Dellacasagrande, J.; Puissant-Lubrano, B.; Apoil, P. A.; Guedj, K.; Abbas, F.; Laffont, S.; Sourdet, S.; Guyonnet, S.; Nourhashemi, F.; Guery, J. C.; Blancher, A. Monocytes are the main source of STING-mediated IFN-alpha production Journal Article In: EBioMedicine, vol. 80, pp. 104047, 2022, ISSN: 2352-3964 (Electronic) 2352-3964 (Linking). @article{RN2018, |
Yang, Cui; Blaize, Gaëtan; Marrocco, Rémi; Rouquié, Nelly; Bories, Cyrielle; Gador, Mylène; Mélique, Suzanne; Joulia, Emeline; Benamar, Mehdi; Dejean, Anne S.; Daniels-Treffandier, Hélène; Love, Paul E.; Fazilleau, Nicolas; Saoudi, Abdelhadi; Lesourne, Renaud THEMIS enhances the magnitude of normal and neuroinflammatory type 1 immune responses by promoting TCR-independent signals Journal Article In: Science Signaling, vol. 15, no. 742, pp. eabl5343, 2022, (Publisher: American Association for the Advancement of Science). @article{yang_themis_2022, |
Han, Mingyu; Cantaloube-Ferrieu, Vincent; Xie, Maorong; Armani-Tourret, Marie; Woottum, Marie; Pagès, Jean-Christophe; Colin, Philippe; Lagane, Bernard; Benichou, Serge HIV-1 cell-to-cell spread overcomes the virus entry block of non-macrophage-tropic strains in macrophages Journal Article In: PLoS pathogens, vol. 18, no. 5, pp. e1010335, 2022, ISSN: 1553-7374. @article{han_hiv-1_2022, Macrophages (MΦ) are increasingly recognized as HIV-1 target cells involved in the pathogenesis and persistence of infection. Paradoxically, in vitro infection assays suggest that virus isolates are mostly T-cell-tropic and rarely MΦ-tropic. The latter are assumed to emerge under CD4+ T-cell paucity in tissues such as the brain or at late stage when the CD4 T-cell count declines. However, assays to qualify HIV-1 tropism use cell-free viral particles and may not fully reflect the conditions of in vivo MΦ infection through cell-to-cell viral transfer. Here, we investigated the capacity of viruses expressing primary envelope glycoproteins (Envs) with CCR5 and/or CXCR4 usage from different stages of infection, including transmitted/founder Envs, to infect MΦ by a cell-free mode and through cell-to-cell transfer from infected CD4+ T cells. The results show that most viruses were unable to enter MΦ as cell-free particles, in agreement with the current view that non-M-tropic viruses inefficiently use CD4 and/or CCR5 or CXCR4 entry receptors on MΦ. In contrast, all viruses could be effectively cell-to-cell transferred to MΦ from infected CD4+ T cells. We further showed that viral transfer proceeded through Env-dependent cell-cell fusion of infected T cells with MΦ targets, leading to the formation of productively infected multinucleated giant cells. Compared to cell-free infection, infected T-cell/MΦ contacts showed enhanced interactions of R5 M- and non-M-tropic Envs with CD4 and CCR5, resulting in a reduced dependence on receptor expression levels on MΦ for viral entry. Altogether, our results show that virus cell-to-cell transfer overcomes the entry block of isolates initially defined as non-macrophage-tropic, indicating that HIV-1 has a more prevalent tropism for MΦ than initially suggested. This sheds light into the role of this route of virus cell-to-cell transfer to MΦ in CD4+ T cell rich tissues for HIV-1 transmission, dissemination and formation of tissue viral reservoirs. |
Argenty, Jérémy; Rouquié, Nelly; Bories, Cyrielle; Mélique, Suzanne; Duplan-Eche, Valérie; Saoudi, Abdelhadi; Fazilleau, Nicolas; Lesourne, Renaud A selective LIS1 requirement for mitotic spindle assembly discriminates distinct Ŧ-cell division mechanisms within the Ŧ-cell lineage Journal Article In: Elife, vol. 11, pp. e80277, 2022, ISSN: 2050-084X. @article{argenty_selective_2022, The ability to proliferate is a common feature of most T-cell populations. However, proliferation follows different cell-cycle dynamics and is coupled to different functional outcomes according to T-cell subsets. Whether the mitotic machineries supporting these qualitatively distinct proliferative responses are identical remains unknown. Here, we show that disruption of the microtubule-associated protein LIS1 in mouse models leads to proliferative defects associated with a blockade of T-cell development after β-selection and of peripheral CD4+ T-cell expansion after antigen priming. In contrast, cell divisions in CD8+ T cells occurred independently of LIS1 following T-cell antigen receptor stimulation, although LIS1 was required for proliferation elicited by pharmacological activation. In thymocytes and CD4+ T cells, LIS1 deficiency did not affect signaling events leading to activation but led to an interruption of proliferation after the initial round of division and to p53-induced cell death. Proliferative defects resulted from a mitotic failure, characterized by the presence of extra-centrosomes and the formation of multipolar spindles, causing abnormal chromosomes congression during metaphase and separation during telophase. LIS1 was required to stabilize dynein/dynactin complexes, which promote chromosome attachment to mitotic spindles and ensure centrosome integrity. Together, these results suggest that proliferative responses are supported by distinct mitotic machineries across T-cell subsets. |
Giang, N.; Villeneuve, T.; Maire, K.; Mejia, J. E.; Guery, J. C.; Pelletier, L.; Savignac, M. PKCalpha interacts with Ca(v) 1.3 calcium channels to promote the Ca(v) 1.2/Ca(v) 1.3 duo tuning Th2 functions Journal Article In: Allergy, 2022, ISSN: 1398-9995 (Electronic) 0105-4538 (Linking). @article{RN2049, |
Giang, N.; Mars, M.; Moreau, M.; Mejia, J. E.; Bouchaud, G.; Magnan, A.; Michelet, M.; Ronsin, B.; Murphy, G. G.; Striessnig, J.; Guery, J. C.; Pelletier, L.; Savignac, M. Separation of the Cav1.2-Cav1.3 calcium channel duo prevents type 2 allergic airway inflammation Journal Article In: Allergy, vol. 77, no. 2, pp. 525-539, 2022, ISSN: 1398-9995 (Electronic) 0105-4538 (Linking). @article{RN1997, |
2021 |
Bertrand R Conde E, Balbino B Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice Journal Article In: Nature Communications, vol. 12, no. 1, pp. 2574, 2021. @article{E2021, |
Darrigues, Julie; Santamaria, Jeremy C.; Galindo-Albarrán, Ariel; Robey, Ellen A.; Joffre, Olivier P.; van Meerwijk, Joost P. M.; Romagnoli, Paola Robust intrathymic development of regulatory T cells in young NOD mice is rapidly restrained by recirculating cells Journal Article In: European Journal of Immunology, 2021, ISSN: 15214141. @article{Darrigues2020b, Regulatory T lymphocytes (Treg) play a vital role in the protection of the organism against autoimmune pathology. It is therefore paradoxical that comparatively large numbers of Treg were found in the thymus of type I diabetes-prone NOD mice. The Treg population in the thymus is composed of newly developing cells and cells that had recirculated from the periphery back to the thymus. We here demonstrate that exceptionally large numbers of Treg develop in the thymus of young, but not adult, NOD mice. Once emigrated from the thymus, an unusually large proportion of these Treg is activated in the periphery, which causes a particularly abundant accumulation of recirculating Treg in the thymus. These cells then rapidly inhibit de novo development of Treg. The proportions of developing Treg thus reach levels similar to or lower than those found in most other, type 1 diabetes-resistant, inbred mouse strains. Thus, in adult NOD mice the particularly large Treg-niche is actually composed of mostly recirculating cells and only few newly developing Treg. |
El Costa, H.; Gouilly, J.; Abravanel, F.; Bahraoui, E.; Peron, J. M.; Kamar, N.; Jabrane-Ferrat, N.; Izopet, J. Effector memory CD8 T cell response elicits Hepatitis E Virus genotype 3 pathogenesis in the elderly Journal Article In: PLoS Pathog, vol. 17, no. 2, pp. e1009367, 2021, ISSN: 1553-7374 (Electronic) 1553-7366 (Linking). @article{RN4b, |
Armani-Tourret, M.; Zhou, Z.; Gasser, R.; Staropoli, I.; Cantaloube-Ferrieu, V.; Benureau, Y.; Garcia-Perez, J.; Perez-Olmeda, M.; Lorin, V.; Puissant-Lubrano, B.; Assoumou, L.; Delaugerre, C.; Lelievre, J. D.; Levy, Y.; Mouquet, H.; Martin-Blondel, G.; Alcami, J.; Arenzana-Seisdedos, F.; Izopet, J.; Colin, P.; Lagane, B. Mechanisms of HIV-1 evasion to the antiviral activity of chemokine CXCL12 indicate potential links with pathogenesis Journal Article In: PLoS Pathog, vol. 17, no. 4, pp. e1009526, 2021, ISSN: 1553-7374 (Electronic) 1553-7366 (Linking). @article{RN3b, |
Blanquart, E.; Mandonnet, A.; Mars, M.; Cenac, C.; Anesi, N.; Mercier, P.; Audouard, C.; Roga, S.; Serrano de Almeida, G.; Bevan, C. L.; Girard, J. P.; Pelletier, L.; Laffont, S.; Guery, J. C. Targeting androgen signaling in ILC2s protects from IL-33-driven lung inflammation, independently of KLRG1 Journal Article In: J Allergy Clin Immunol, 2021, ISSN: 1097-6825 (Electronic) 0091-6749 (Linking). @article{RN1947, |
Cenac, C.; Ducatez, M.; Guery, J. C. Hydroxychloroquine inhibits proteolytic processing of endogenous TLR7 protein in human primary plasmacytoid dendritic cells Journal Article In: Eur J Immunol, 2021, ISSN: 1521-4141 (Electronic) 0014-2980 (Linking). @article{RN1956, |
Osma-Garcia, I. C.; Capitan-Sobrino, D.; Mouysset, M.; Bell, S. E.; Lebeurrier, M.; Turner, M.; Diaz-Munoz, M. D. The RNA-binding protein HuR is required for maintenance of the germinal centre response Journal Article In: Nat Commun, vol. 12, no. 1, pp. 6556, 2021, ISSN: 2041-1723 (Electronic) 2041-1723 (Linking). @article{RN2, |
Stackowicz, J.; Gaudenzio, N.; Serhan, N.; Conde, E.; Godon, O.; Marichal, T.; Starkl, P.; Balbino, B.; Roers, A.; Bruhns, P.; Jonsson, F.; Moguelet, P.; Georgin-Lavialle, S.; Broderick, L.; Hoffman, H. M.; Galli, S. J.; Reber, L. L. Neutrophil-specific gain-of-function mutations in Nlrp3 promote development of cryopyrin-associated periodic syndrome Journal Article In: J Exp Med, vol. 218, no. 10, 2021, ISSN: 1540-9538 (Electronic) 0022-1007 (Linking). @article{RN2330, |
2020 |
Briand-Mésange, Fabienne; Pons, Véronique; Allart, Sophie; Masquelier, Julien; Chicanne, Gaëtan; Beton, Nicolas; Payrastre, Bernard; Muccioli, Giulio G.; Ausseil, Jérôme; Davignon, Jean Luc; Salles, Jean Pierre; Chap, Hugues Glycerophosphodiesterase 3 (GDE3) is a lysophosphatidylinositol-specific ectophospholipase C acting as an endocannabinoid signaling switch Journal Article In: Journal of Biological Chemistry, vol. 295, no. 46, pp. 15767–15781, 2020, ISSN: 1083351X. @article{Briand-Mesange2020, Endocannabinoid signaling plays a regulatory role in various (neuro)biological functions. 2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid, and although its canonical biosynthetic pathway involving phosphoinositide-specific phospholipase C and diacylglycerol lipase a is known, alternative pathways remain unsettled. Here, we characterize a non-canonical pathway implicating glycerophosphodiesterase 3 (GDE3, from GDPD2 gene). Human GDE3 expressed in HEK293T cell membranes catalyzed the conversion of lysophosphatidylinositol (LPI) into monoacylglycerol and inositol-1-phosphate. The enzyme was equally active against 1-acyl and 2-acyl LPI. When using 2-acyl LPI, where arachidonic acid is the predominant fatty acid, LC-MS analysis identified 2-AG as the main product of LPI hydrolysis by GDE3. Furthermore, inositol-1-phosphate release into the medium occurred upon addition of LPI to intact cells, suggesting that GDE3 is actually an ecto-lysophospholipase C. In cells expressing G-protein–coupled receptor GPR55, GDE3 abolished 1-acyl LPI–induced signaling. In contrast, upon simultaneous expression of GDE3 and cannabinoid receptor CB2, 2-acyl LPI evoked the same signal as that induced by 2-AG. These data strongly suggest that, in addition to degrading the GPR55 LPI ligand, GDE3 can act as a switch between GPR55 and CB2 signaling. Coincident with a major expression of both GDE3 and CB2 in the spleen, spleens from transgenic mice lacking GDE3 displayed doubling of LPI content compared with WT mice. Decreased production of 2-AG in whole spleen was also observed, supporting the in vivo relevance of our findings. These data thus open a new research avenue in the field of endocannabinoid generation and reinforce the view of GPR55 and LPI being genuine actors of the endocannabinoid system. |
Balbino, B; Herviou, P; o Godon,; Stackowicz, J; Goff, O R; Iannascoli, B; Sterlin, D; Brûlé, S; Millot, G A; Harris, F M; Voronina, V A; Nadeau, K C; Macdonald, L E; Murphy, A J; Bruhns, P; Reber, L L The anti-IgE mAb omalizumab induces adverse reactions by engaging Fcγ receptors. Journal Article In: J Clin Invest, vol. 130, no. 3, pp. 1330-1335, 2020. @article{B2020, |
Meixiong, James; Basso, Lilian; Dong, Xinzhong; Gaudenzio, Nicolas Nociceptor-Mast Cell Sensory Clusters as Regulators of Skin Homeostasis. Journal Article In: Trends in neurosciences, vol. 43, no. 3, pp. 130–132, 2020, ISSN: 1878-108X (Electronic). @article{Meixiong2020, Recent studies revealed the existence of unique functional links between mast cells and nociceptors in the skin. Here, we propose that mast cells and nociceptors form a single regulatory unit in both physiology and disease. In this model, MrgprB2/X2 signaling is a primary mechanism by which mast cells functionally interact with nociceptors to form specialized neuroimmune clusters that regulate pain, inflammation, and itch. |
Hassan, A.; Wlodarczyk, M. F.; Benamar, M.; Bassot, E.; Salvioni, A.; Kassem, S.; Berry, A.; Saoudi, A.; Blanchard, N. A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent Manner Journal Article In: mBio, vol. 11, no. 2, 2020, (doi: 10.1128/mBio.03394-19.). @article{c, Coinfections shape immunity and influence the development of inflammatory diseases, resulting in detrimental or beneficial outcome. Coinfections with concurrent Plasmodium species can alter malaria clinical evolution, and malaria infection itself can modulate autoimmune reactions. Yet, the underlying mechanisms remain ill defined. Here, we demonstrate that the protective effects of some rodent malaria strains on T cell-mediated inflammatory pathologies are due to an RNA virus cohosted in malaria-parasitized blood. We show that live and extracts of blood parasitized by Plasmodium berghei K173 or Plasmodium yoelii 17X YM, protect against P. berghei ANKA-induced experimental cerebral malaria (ECM) and myelin oligodendrocyte glycoprotein (MOG)/complete Freund's adjuvant (CFA)-induced experimental autoimmune encephalomyelitis (EAE), and that protection is associated with a strong type I interferon (IFN-I) signature. We detected the presence of the RNA virus lactate dehydrogenase-elevating virus (LDV) in the protective Plasmodium stabilates and we established that LDV infection alone was necessary and sufficient to recapitulate the protective effects on ECM and EAE. In ECM, protection resulted from an IFN-I-mediated reduction in the abundance of splenic conventional dendritic cell and impairment of their ability to produce interleukin (IL)-12p70, leading to a decrease in pathogenic CD4(+) Th1 responses. In EAE, LDV infection induced IFN-I-mediated abrogation of IL-23, thereby preventing the differentiation of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing encephalitogenic CD4(+) T cells. Our work identifies a virus cohosted in several Plasmodium stabilates across the community and deciphers its major consequences on the host immune system. More generally, our data emphasize the importance of considering contemporaneous infections for the understanding of malaria-associated and autoimmune diseases.IMPORTANCE Any infection modifies the host immune status, potentially ameliorating or aggravating the pathophysiology of a simultaneous inflammatory condition. In the course of investigating how malaria infection modulates the severity of contemporaneous inflammatory diseases, we identified a nonpathogenic mouse virus in stabilates of two widely used rodent parasite lines: Plasmodium berghei K173 and Plasmodium yoelii 17X YM. We established that the protective effects of these Plasmodium lines on cerebral malaria and multiple sclerosis are exclusively due to this virus. The virus induces a massive type I interferon (IFN-I) response and causes quantitative and qualitative defects in the ability of dendritic cells to promote pathogenic T cell responses. Beyond revealing a possible confounding factor in rodent malaria models, our work uncovers some bases by which a seemingly innocuous viral (co)infection profoundly changes the immunopathophysiology of inflammatory diseases. |
Lamsoul, Isabelle; Dupré, Loïc; Lutz, Pierre G. Molecular Tuning of Filamin A Activities in the Context of Adhesion and Migration Journal Article In: Front Cell Dev Biol, vol. 8, pp. 591323, 2020, ISSN: 2296-634X. @article{lamsoul_molecular_2020, The dynamic organization of actin cytoskeleton meshworks relies on multiple actin-binding proteins endowed with distinct actin-remodeling activities. Filamin A is a large multi-domain scaffolding protein that cross-links actin filaments with orthogonal orientation in response to various stimuli. As such it plays key roles in the modulation of cell shape, cell motility, and differentiation throughout development and adult life. The essentiality and complexity of Filamin A is highlighted by mutations that lead to a variety of severe human disorders affecting multiple organs. One of the most conserved activity of Filamin A is to bridge the actin cytoskeleton to integrins, thereby maintaining the later in an inactive state. We here review the numerous mechanisms cells have developed to adjust Filamin A content and activity and focus on the function of Filamin A as a gatekeeper to integrin activation and associated adhesion and motility. |
Azar, P.; Mejía, J. E.; Cenac, C.; Shaiykova, A.; Youness, A.; Laffont, S.; Essat, A.; Izopet, J.; Passaes, C.; Müller-Trutwin, M.; Delobel, P.; Meyer, L.; Guéry, J. C. TLR7 dosage polymorphism shapes interferogenesis and HIV-1 acute viremia in women Journal Article In: JCI Insight, vol. 5, no. 12, 2020, ISSN: 2379-3708. @article{RN1940, |
Raymond, Stéphanie; Piffaut, Marie; Bigot, Jonathan; Cazabat, Michelle; Montes, Brigitte; Bertrand, Kevin; Martin-Blondel, Guillaume; Izopet, Jacques; Delobel, Pierre Sexual transmission of an extensively drug-resistant HIV-1 strain Journal Article In: The Lancet HIV, vol. 7, no. 8, pp. e529–e530, 2020, ISSN: 23523018. @article{raymond_sexual_2020, |
Nayrac, Manon; Requena, Mary; Loiseau, Claire; Cazabat, Michelle; Suc, Bertrand; Carrere, Nicolas; Barange, Karl; Alric, Laurent; Martin-Blondel, Guillaume; Izopet, Jacques; Delobel, Pierre In: Mucosal Immunology, vol. 14, no. 1, pp. 219–228, 2020, ISSN: 1933-0219, 1935-3456. @article{nayrac_th22_2020, |
Marion, Olivier; Lhomme, Sebastien; Nayrac, Manon; Dubois, Martine; Pucelle, Mélanie; Requena, Mary; Migueres, Marion; Abravanel, Florence; Peron, Jean Marie; Carrere, Nicolas; Suc, Bertrand; Delobel, Pierre; Kamar, Nassim; Izopet, Jacques Hepatitis E virus replication in human intestinal cells Journal Article In: Gut, vol. 69, no. 5, pp. 901–910, 2020, ISSN: 0017-5749, 1468-3288. @article{marion_hepatitis_2020, |
Chen, Qian; Gouilly, Jordi; Ferrat, Yann J.; Espino, Ana; Glaziou, Quentin; Cartron, Géraldine; El Costa, Hicham; Al-Daccak, Reem; Jabrane-Ferrat, Nabila Metabolic reprogramming by Zika virus provokes inflammation in human placenta Journal Article In: Nature Communications, vol. 11, no. 1, 2020, ISSN: 2041-1723. @article{chen_metabolic_2020, |
Malviya, M.; Saoudi, A.; Bauer, J.; Fillatreau, S.; Liblau, R. Treatment of experimental autoimmune encephalomyelitis with engineered bi-specific Foxp3+ regulatory CD4+ T cells Journal Article In: J Autoimmun, vol. 108, pp. 102401, 2020, ISSN: 1095-9157 (Electronic) 0896-8411 (Linking). @article{RN54, |
2019 |
Serhan, N.; Basso, L.; Sibilano, R.; Petitfils, C.; Meixiong, J.; Bonnart, C.; Reber, L L.; Marichal, T.; Starkl, P.; Cenac, N.; Dong, X.; Tsai, M.; Galli, S J.; Gaudenzio, N. House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation Journal Article In: Nat Immunol, vol. 20, no. 11, pp. 1435-1443, 2019. @article{N2019, |
Adoue, V; Binet, B; Malbec, A; Fourquet, J; Romagnoli, P; van Meerwijk, J P M; Amigorena, S; Joffre, O P The Histone Methyltransferase SETDB1 Controls T Helper Cell Lineage Integrity by Repressing Endogenous Retroviruses. Journal Article In: Immunity, vol. 50, pp. 629–644, 2019. @article{Adoue2019, Upon activation, naive CD4+ T cells differentiate into distinct T cell subsets via processes reliant on epigenetically regulated, lineage-specific developmental programs. Here, we examined the function of the histone methyltransferase SETDB1 in T helper (Th) cell differentiation. Setdb1-/- naive CD4+ T cells exhibited exacerbated Th1 priming, and when exposed to a Th1-instructive signal, Setdb1-/- Th2 cells crossed lineage boundaries and acquired a Th1 phenotype. SETDB1 did not directly control Th1 gene promoter activity but relied instead on deposition of the repressive H3K9me3 mark at a restricted and cell-type-specific set of endogenous retroviruses (ERVs) located in the vicinity of genes involved in immune processes. Refined bioinformatic analyses suggest that these retrotransposons regulate Th1 gene cis-regulatory elements or act as Th1 gene enhancers. Thus, H3K9me3 deposition by SETDB1 ensures Th cell lineage integrity by repressing a repertoire of ERVs that have been exapted into cis-regulatory modules to shape and control the Th1 gene network. |
Domingo, Cristina; Fraissinet, Juliane; Ansah, Patrick O.; Kelly, Corey; Bhat, Niranjan; Sow, Samba O.; Mejía, José E. Long-term immunity against yellow fever in children vaccinated during infancy: a longitudinal cohort study Journal Article In: Lancet Infect Dis, 2019, ISSN: 1473-3099. @article{RN3090, Background. A single dose of vaccine against yellow fever is routinely administered to infants aged 9–12 months under the Expanded Programme on Immunization, but the long-term outcome of vaccination in this age group is unknown. We aimed to evaluate the long-term persistence of neutralising antibodies to yellow fever virus following routine vaccination in infancy. Methods. We did a longitudinal cohort study, using a microneutralisation assay to measure protective antibodies against yellow fever in Malian and Ghanaian children vaccinated around age 9 months and followed up for 4·5 years (Mali), or 2·3 and 6·0 years (Ghana). Healthy children with available day-0 sera, a complete follow-up history, and no record of yellow fever revaccination were included; children seropositive for yellow fever at baseline were excluded. We standardised antibody concentrations with reference to the yellow fever WHO International Standard. Findings. We included 587 Malian and 436 Ghanaian children vaccinated between June 5, 2009, and Dec 26, 2012. In the Malian group, 296 (50·4%, 95% CI 46·4–54·5) were seropositive (antibody concentration ≥0·5 IU/mL) 4·5 years after vaccination. Among the Ghanaian children, 121 (27·8%, 23·5–32·0) were seropositive after 2·3 years. These results show a large decrease from the proportions of seropositive infants 28 days after vaccination, 96·7% in Mali and 72·7% in Ghana, reported by a previous study of both study populations. The number of seropositive children increased to 188 (43·1%, 95% CI 38·5–47·8) in the Ghanaian group 6·0 years after vaccination, but this result might be confounded by unrecorded revaccination or natural infection with wild yellow fever virus during a 2011–12 outbreak in northern Ghana. Interpretation. Rapid waning of immunity during the early years after vaccination of 9-month-old infants argues for a revision of the single-dose recommendation for this target population in endemic countries. The short duration of immunity in many vaccinees suggests that booster vaccination is necessary to meet the 80% population immunity threshold for prevention of yellow fever outbreaks. |
Piliponsky, A. M.; Shubin, N. J.; Lahiri, A. K.; Truong, P.; Clauson, M.; Niino, K.; Tsuha, A. L.; Nedospasov, S. A.; Karasuyama, H.; Reber, L. L.; Tsai, M.; Mukai, K.; Galli, S. J. Basophil-derived tumor necrosis factor can enhance survival in a sepsis model in mice Journal Article In: Nat Immunol, vol. 20, no. 2, pp. 129-140, 2019, ISSN: 1529-2916 (Electronic) 1529-2908 (Linking). @article{RN1b, |
2018 |
Rosa, N.; Triffaux, E.; Robert, V.; Mars, M.; Klein, M.; Bouchaud, G.; Canivet, A.; Magnan, A.; Guery, J. C.; Pelletier, L.; Savignac, M. In: J Allergy Clin Immunol, vol. 142, no. 3, pp. 892-903, 2018, ISSN: 1097-6825 (Electronic) 0091-6749 (Linking). @article{RN24, |
Souyris, M.; Cenac, C.; Azar, P.; Daviaud, D.; Canivet, A.; Grunenwald, S.; Pienkowski, C.; Chaumeil, J.; Mejia, J. E.; Guery, J. C. TLR7 escapes X chromosome inactivation in immune cells Journal Article In: Sci Immunol, vol. 3, no. 19, 2018, ISSN: 2470-9468 (Electronic) 2470-9468 (Linking), (In the top 5% of all research outputs scored by Altmetric. http://www.altmetric.com/details/32261033). @article{RN25b, |
Eissmann, M. F.; Dijkstra, C.; Wouters, M. A.; Baloyan, D.; Mouradov, D.; Nguyen, P. M.; Davalos-Salas, M.; Putoczki, T. L.; Sieber, O. M.; Mariadason, J. M.; Ernst, M.; Masson, F. Interleukin 33 Signaling Restrains Sporadic Colon Cancer in an Interferon-gamma-Dependent Manner Journal Article In: Cancer Immunol Res, vol. 6, no. 4, pp. 409-421, 2018, ISSN: 2326-6074 (Electronic) 2326-6066 (Linking). @article{RN1b, |
Houmadi, R.; Guipouy, D.; Rey-Barroso, J.; Vasconcelos, Z.; Cornet, J.; Manghi, M.; Destainville, N.; Valitutti, S.; Allart, S.; Dupre, L. The Wiskott-Aldrich Syndrome Protein Contributes to the Assembly of the LFA-1 Nanocluster Belt at the Lytic Synapse Journal Article In: Cell Rep, vol. 22, no. 4, pp. 979-991, 2018, ISSN: 2211-1247 (Electronic). @article{RN3b, |
Gaud, G.; Lesourne, R.; Love, P. E. Regulatory mechanisms in T cell receptor signalling Journal Article In: Nat Rev Immunol, 2018, ISSN: 1474-1741 (Electronic) 1474-1733 (Linking). @article{RN1b, |
Colin, P.; Zhou, Z.; Staropoli, I.; Garcia-Perez, J.; Gasser, R.; Armani-Tourret, M.; Benureau, Y.; Gonzalez, N.; Jin, J.; Connell, B. J.; Raymond, S.; Delobel, P.; Izopet, J.; Lortat-Jacob, H.; Alcami, J.; Arenzana-Seisdedos, F.; Brelot, A.; Lagane, B. CCR5 structural plasticity shapes HIV-1 phenotypic properties Journal Article In: PLoS Pathog, vol. 14, no. 12, pp. e1007432, 2018, ISSN: 1553-7374 (Electronic) 1553-7366 (Linking). @article{RN859, |
2017 |
Tauber, Maïthé; Boulanouar, Kader; Diene, Gwenaelle; Çabal-Berthoumieu, Sophie; Ehlinger, Virginie; Fichaux-Bourin, Pascale; Molinas, Catherine; Faye, Sandy; Valette, Marion; Pourrinet, Jeanne; Cessans, Catie; Viaux-Sauvelon, Sylvie; Bascoul, Céline; Guedeney, Antoine; Delhanty, Patric; Geenen, Vincent; Martens, Henri; Muscatelli, Françoise; Cohen, David; Consoli, Angèle; Payoux, Pierre; Arnaud, Catherine; Salles, Jean-Pierre The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader–Willi Syndrome Journal Article In: PEDIATRICS, vol. 139, no. 2, pp. e2 0162976, 2017. @article{RN10b, |
Asrir, A.; Aloulou, M.; Gador, M.; Perals, C.; Fazilleau, N. Interconnected subsets of memory follicular helper T cells have different effector functions Journal Article In: Nat Commun, vol. 8, no. 1, pp. 847, 2017, ISSN: 2041-1723 (Electronic) 2041-1723 (Linking). @article{RN2b, |
Duguet, F.; Locard-Paulet, M.; Marcellin, M.; Chaoui, K.; Bernard, I.; Andreoletti, O.; Lesourne, R.; Burlet-Schiltz, O.; Gonzalez de Peredo, A.; Saoudi, A. Proteomic Analysis of Regulatory T Cells Reveals the Importance of Themis1 in the Control of Their Suppressive Function Journal Article In: Mol Cell Proteomics, vol. 16, no. 8, pp. 1416-1432, 2017, ISSN: 1535-9484 (Electronic) 1535-9476 (Linking). @article{RN4b, |
Laffont, Sophie; Blanquart, Eve; Savignac, Magali; Cenac, Claire; Laverny, Gilles; Metzger, Daniel; Girard, Jean-Philippe; Belz, Gabrielle T; Pelletier, Lucette; Seillet, Cyril; Guery, Jean-Charles Androgen signaling negatively controls group 2 innate lymphoid cells Journal Article In: J Exp Med, vol. 214, no. 6, pp. 1581-1592, 2017, ISSN: 1540-9538 (Electronic) 0022-1007 (Linking). @article{RN3, |
Yshii, L. M.; Hohlfeld, R.; Liblau, R. S. Inflammatory CNS disease caused by immune checkpoint inhibitors: status and perspectives Journal Article In: Nat Rev Neurol, vol. 13, no. 12, pp. 755-763, 2017, ISSN: 1759-4766 (Electronic) 1759-4758 (Linking). @article{RN5b, |
Joulia, R.; Mailhol, C.; Valitutti, S.; Didier, A.; Espinosa, E. Direct monitoring of basophil degranulation by using avidin-based probes Journal Article In: J Allergy Clin Immunol, 2017, ISSN: 1097-6825 (Electronic) 0091-6749 (Linking). @article{RN16, |