-
1تقرير
المؤلفون: Miatello, Jordi, Lukaszewicz, Anne-Claire, Faivre, Valérie, Hua, Stéphane, Martinet, Kim Zita, Bourgeois, Christine, Quintana-Murci, Lluis, Payen, Didier, Boniotto, Michele, Tissières, Pierre
المساهمون: Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Edouard Herriot CHU - HCL, Hospices Civils de Lyon (HCL), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Paléospace, Infectious Diseases Models for Innovative Therapies (IDMIT), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de neurologie Le Kremlin Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre, Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
المصدر: https://hal.science/hal-04271615Test ; 2023.
مصطلحات موضوعية: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
الوصف: Monocyte HLA-DR is an increasingly recognized markers of sepsis-induced immunodepression, but its regulatory mechanisms remain poorly understood in sepsis. Several evidence for positive selection on the 5’ promoter region of HLA class II transactivator ( CIITA ) gene, the master regulator of MHC class II, have been gathered in the European population, and its role in sepsis has never been demonstrated, whilst suggested in autoimmune disease. We aim to describe the effect of rs3087456 polymorphism, localized on CIITA promoter III (pIII), on mortality of patients with septic shock, and investigate the mechanisms regulating HLA-DR expression. Genotyping of 203 patients with septic shock showed that, in A dominant model, GG genotype was associated with 28-day mortality (OR 2.29; 95%CI: 1.01 to 5.22; P = 0.043). Monocyte HLA-DR remained low in patients with GG genotype whereas it increases as early as at the end of the first week in intensive care in patients with AA or AG genotype. Using site-directed mutagenesis, in vitro reporter gene promoter activity of the pIII was decreased in GG genotype in monocyte cell line. Interferon-γ (IFN-γ) restored pIII activity in GG genotype as well as restore, in ex vivo experiment in healthy volunteers, CIITA pIII expression of GG genotype. Hereby, we demonstrated that rs3087456, a positively selected polymorphism of CIITA proximal promoter, significantly impact monocyte HLA-DR expression in patients with septic shock through CIITA promoter activity, that can be rescued using IFN-γ, offering a new perspective in genetic susceptibility to sepsis and targeted immunomodulatory therapy. Keypoints CIITA G-286A polymorphism reduces promotor activity and significantly impact monocyte HLA-DR expression and mortality in septic shock Downregulatory effects of CIITA G-286A polymorphism on monocyte HLA-DR expression can be reverse by IFN-γ in patients with septic shock
العلاقة: hal-04271615; https://hal.science/hal-04271615Test; MEDRXIV: 2021.02.19.21252097
-
2دورية أكاديمية
المؤلفون: Martinet, Kim, Zita, Bloquet, Stéphane, Bourgeois, Christine
المساهمون: Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Animalerie centrale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the ANRS (Agence Nationale de la Recherche contre le SIDA et les hépatites C), la Fondation pour la Recherche Médicale (FRM) and benefited from donations of the CIC bank (Crédit Industriel et Commercial) and Pericles consulting group.
المصدر: Immunity & Ageing ; https://inserm.hal.science/inserm-00991192Test ; Immunity & Ageing, 2014, 11 (1), pp.8
مصطلحات موضوعية: Immunology, T cell, T cell lymphopenia, T cell homeostasis, Immunosenescence, Ageing, Aging, Age, GALT, MALT, CD4 T cell lymphopenia, CD4 T cell homeostasi, [SDV.IMM]Life Sciences [q-bio]/Immunology
الوصف: International audience ; Background CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue (GALT), a crucial site of CD4 T cell accumulation. Results Primary, secondary and tertiary lymphoid organs of C57BL/6 animals were analysed at three intervals of ages: 2 to 6 months (young), 10 to 14 months (middle-aged) and 22 to 26 months (old). We confirmed that ageing preferentially impacted CD4 T cell compartment in secondary lymphoid organs. Importantly, a different picture emerged from gut associated mucosal sites: during ageing, CD4 T cell accumulation was progressively developing in colon and small intestine lamina propria and Peyer's patches. Similar trend was also observed in middle-aged SJL/B6 F1 mice. Interestingly, an inverse correlation was detected between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria of C57BL/6 mice whereas no increase in proliferation rate of GALT CD4 T cells was detected. In contrast to GALT, no CD4 T cell accumulation was detected in lungs and liver in middle-aged animals. Finally, the concomitant accumulation of CD4 T cell in GALT and depletion in secondary lymphoid organs during ageing was detected both in male and female animals. Conclusions Our data thus demonstrate that T cell lymphopenia in secondary lymphoid organs currently associated to ageing is not sustained in gut or lung mucosa associated lymphoid tissues or non-lymphoid sites such as the liver. The inverse correlation between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria and the absence of overt proliferation in GALT suggest that marked CD4 T cell decay in secondary ...
العلاقة: inserm-00991192; https://inserm.hal.science/inserm-00991192Test; https://inserm.hal.science/inserm-00991192/documentTest; https://inserm.hal.science/inserm-00991192/file/1742-4933-11-8.pdfTest
-
3دورية أكاديمية
المؤلفون: Simonetta, Federico, Gestermann, Nicolas, Martinet, Kim Zita, Boniotto, Michele, Tissières, Pierre, Seddon, Benedict, Bourgeois, Christine
المساهمون: Zenclussen, Ana Claudia
المصدر: PLoS ONE ; volume 7, issue 5, page e36596 ; ISSN 1932-6203
-
4دورية أكاديمية
المؤلفون: Simonetta, Federico, Gestermann, Nicolas, Martinet, Kim Zita, Boniotto, Michele, Tissières, Pierre, Seddon, Benedict, Bourgeois, Christine
المصدر: PLoS ONE; May2012, Vol. 7 Issue 5, p1-9, 9p
مصطلحات موضوعية: INTERLEUKIN-7, T cells, CELLULAR control mechanisms, HOMEOSTASIS, IMMUNE response, AUTOIMMUNITY
مستخلص: Mechanisms governing peripheral CD4+ FOXP3+ regulatory T cells (Treg) survival and homeostasis are multiple suggesting tight and complex regulation of regulatory T cells homeostasis. Some specific factors, such as TGF-β, interleukin-2 (IL-2) and B7 costimulatory molecules have been identified as essentials for maintenance of the peripheral Treg compartment. Conversely, Treg dependency upon classical T cell homeostatic factors such as IL-7 is still unclear. In this work, we formally investigated the role of IL-7 in Treg homeostasis in vivo in murine models. We demonstrated that IL-7 availability regulated the size of peripheral Treg cell pool and thus paralleled the impact of IL-7 on conventional T cell pool. Moreover, we showed that IL-7 administration increased Treg cell numbers by inducing thymic-independent Treg peripheral expansion. Importantly the impact of IL-7 on Treg expansion was detected whether conventional T cells were present or absent as IL-7 directly participates to the peripheral expansion of Treg after adoptive transfer into lymphopenic hosts. Our results definitively identify IL-7 as a central factor contributing to Treg peripheral homeostasis, thus reassembling Treg to other T cell subsets in respect of their need for IL-7 for their peripheral maintenance. [ABSTRACT FROM AUTHOR]
: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
النص الكامل