Emmanuelle Godefroy, Patrice Chevallier, Fabienne Haspot, Caroline Vignes, Véronique Daguin, Sylvia Lambot, Margaux Verdon, Margaux De Seilhac, Valentin Letailleur, Anne Jarry, Annabelle Pédron, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Marie-Anne Vibet, Maxence Mougon, Amandine Bourgeois, Maxime Jullien, Francine Jotereau, Frédéric Altare
{"title":"Human gut microbiota-reactive DP8a regulatory T cells prevent acute graft-versus-host disease in a CD73-dependent manner.","authors":"Emmanuelle Godefroy, Patrice Chevallier, Fabienne Haspot, Caroline Vignes, Véronique Daguin, Sylvia Lambot, Margaux Verdon, Margaux De Seilhac, Valentin Letailleur, Anne Jarry, Annabelle Pédron, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Marie-Anne Vibet, Maxence Mougon, Amandine Bourgeois, Maxime Jullien, Francine Jotereau, Frédéric Altare","doi":"10.1172/jci.insight.179458","DOIUrl":null,"url":null,"abstract":"<p><p>Graft-versus-host disease (GvHD) is a life-threatening complication frequently occurring following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since gut microbiota and regulatory T cells (Tregs) are believed to play roles in GvHD prevention, we investigated whether DP8a Tregs, which we have previously described to harbor a TCR-specificity for the gut commensal Faecalibacterium prausnitzii, could protect against GvHD, thereby linking microbiota and its effect on GvHD. We observed a decrease in CD73+ DP8α Treg frequency in allo-HSCT patients at 1-month post-transplantation, which was associated with aGvHD development at 1-month post-transplantation, as compared to aGvHD-free patients, without being correlated to hematological disease's relapse. Importantly, CD73 activity was shown to be critical for DP8αTreg suppressive function. Moreover, the frequency of host-reactive DP8α Tregs was also lower in aGvHD patients, as compared to aGvHD-free patients, which could embody a protective mechanism responsible for the maintenance of these cell subset in GvHD-free patients. We also showed that human DP8α Tregs protected mice against xeno-GvHD through limiting deleterious inflammation and preserving gut integrity. Altogether, these results demonstrated that human DP8α Tregs mediate aGvHD prevention in a CD73-dependent manner, likely through host-reactivity, advocating for the use of these cells for the development of innovative therapeutic strategies to preclude aGvHD-related inflammation.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":null,"pages":null},"PeriodicalIF":6.3000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCI insight","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1172/jci.insight.179458","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Graft-versus-host disease (GvHD) is a life-threatening complication frequently occurring following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since gut microbiota and regulatory T cells (Tregs) are believed to play roles in GvHD prevention, we investigated whether DP8a Tregs, which we have previously described to harbor a TCR-specificity for the gut commensal Faecalibacterium prausnitzii, could protect against GvHD, thereby linking microbiota and its effect on GvHD. We observed a decrease in CD73+ DP8α Treg frequency in allo-HSCT patients at 1-month post-transplantation, which was associated with aGvHD development at 1-month post-transplantation, as compared to aGvHD-free patients, without being correlated to hematological disease's relapse. Importantly, CD73 activity was shown to be critical for DP8αTreg suppressive function. Moreover, the frequency of host-reactive DP8α Tregs was also lower in aGvHD patients, as compared to aGvHD-free patients, which could embody a protective mechanism responsible for the maintenance of these cell subset in GvHD-free patients. We also showed that human DP8α Tregs protected mice against xeno-GvHD through limiting deleterious inflammation and preserving gut integrity. Altogether, these results demonstrated that human DP8α Tregs mediate aGvHD prevention in a CD73-dependent manner, likely through host-reactivity, advocating for the use of these cells for the development of innovative therapeutic strategies to preclude aGvHD-related inflammation.
期刊介绍:
JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.