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Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation
Gut microbiota dysbiosis is associated with inflammatory bowel diseases and with cardiometabolic, neurological, and autoimmune diseases. Gut microbiota composition has a direct effect on the immune system, and vice versa, and it has a particular effect on Treg homeostasis. Low-dose IL-2 (IL-2(LD)) s...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536277/ https://www.ncbi.nlm.nih.gov/pubmed/35917175 http://dx.doi.org/10.1172/jci.insight.159406 |
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author | Tchitchek, Nicolas Nguekap Tchoumba, Otriv Pires, Gabriel Dandou, Sarah Campagne, Julien Churlaud, Guillaume Fourcade, Gwladys Hoffmann, Thomas W. Strozzi, Francesco Gaal, Camille Bonny, Christophe Le Chatelier, Emmanuelle Erlich, Stanislav Dusko Sokol, Harry Klatzmann, David |
author_facet | Tchitchek, Nicolas Nguekap Tchoumba, Otriv Pires, Gabriel Dandou, Sarah Campagne, Julien Churlaud, Guillaume Fourcade, Gwladys Hoffmann, Thomas W. Strozzi, Francesco Gaal, Camille Bonny, Christophe Le Chatelier, Emmanuelle Erlich, Stanislav Dusko Sokol, Harry Klatzmann, David |
author_sort | Tchitchek, Nicolas |
collection | PubMed |
description | Gut microbiota dysbiosis is associated with inflammatory bowel diseases and with cardiometabolic, neurological, and autoimmune diseases. Gut microbiota composition has a direct effect on the immune system, and vice versa, and it has a particular effect on Treg homeostasis. Low-dose IL-2 (IL-2(LD)) stimulates Tregs and is a promising treatment for autoimmune and inflammatory diseases. We aimed to evaluate the impact of IL-2(LD) on gut microbiota and correlatively on the immune system. We used 16S ribosomal RNA profiling and metagenomics to characterize gut microbiota of mice and humans treated or not with IL-2(LD). We performed fecal microbiota transplantation (FMT) from IL-2(LD)–treated to naive recipient mice and evaluated its effects in models of gut inflammation and diabetes. IL-2(LD) markedly affected gut microbiota composition in mice and humans. Transfer of an IL-2–tuned microbiota by FMT protected C57BL/6J mice from dextran sulfate sodium–induced colitis and prevented diabetes in NOD mice. Metagenomic analyses highlighted a role for several species affected by IL-2(LD) and for microbial pathways involved in the biosynthesis of amino acids, short-chain fatty acids, and L-arginine. Our results demonstrate that IL-2(LD) induced changes in gut microbiota that are involved in the immunoregulatory effects of IL-2(LD) and suggest a crosstalk between Tregs and gut microbiota. These results provide potentially novel insight for understanding the mode of action of Treg-directed therapies. |
format | Online Article Text |
id | pubmed-9536277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-95362772022-10-07 Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation Tchitchek, Nicolas Nguekap Tchoumba, Otriv Pires, Gabriel Dandou, Sarah Campagne, Julien Churlaud, Guillaume Fourcade, Gwladys Hoffmann, Thomas W. Strozzi, Francesco Gaal, Camille Bonny, Christophe Le Chatelier, Emmanuelle Erlich, Stanislav Dusko Sokol, Harry Klatzmann, David JCI Insight Research Article Gut microbiota dysbiosis is associated with inflammatory bowel diseases and with cardiometabolic, neurological, and autoimmune diseases. Gut microbiota composition has a direct effect on the immune system, and vice versa, and it has a particular effect on Treg homeostasis. Low-dose IL-2 (IL-2(LD)) stimulates Tregs and is a promising treatment for autoimmune and inflammatory diseases. We aimed to evaluate the impact of IL-2(LD) on gut microbiota and correlatively on the immune system. We used 16S ribosomal RNA profiling and metagenomics to characterize gut microbiota of mice and humans treated or not with IL-2(LD). We performed fecal microbiota transplantation (FMT) from IL-2(LD)–treated to naive recipient mice and evaluated its effects in models of gut inflammation and diabetes. IL-2(LD) markedly affected gut microbiota composition in mice and humans. Transfer of an IL-2–tuned microbiota by FMT protected C57BL/6J mice from dextran sulfate sodium–induced colitis and prevented diabetes in NOD mice. Metagenomic analyses highlighted a role for several species affected by IL-2(LD) and for microbial pathways involved in the biosynthesis of amino acids, short-chain fatty acids, and L-arginine. Our results demonstrate that IL-2(LD) induced changes in gut microbiota that are involved in the immunoregulatory effects of IL-2(LD) and suggest a crosstalk between Tregs and gut microbiota. These results provide potentially novel insight for understanding the mode of action of Treg-directed therapies. American Society for Clinical Investigation 2022-09-08 /pmc/articles/PMC9536277/ /pubmed/35917175 http://dx.doi.org/10.1172/jci.insight.159406 Text en © 2022 Tchitchek et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Tchitchek, Nicolas Nguekap Tchoumba, Otriv Pires, Gabriel Dandou, Sarah Campagne, Julien Churlaud, Guillaume Fourcade, Gwladys Hoffmann, Thomas W. Strozzi, Francesco Gaal, Camille Bonny, Christophe Le Chatelier, Emmanuelle Erlich, Stanislav Dusko Sokol, Harry Klatzmann, David Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation |
title | Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation |
title_full | Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation |
title_fullStr | Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation |
title_full_unstemmed | Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation |
title_short | Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation |
title_sort | low-dose il-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536277/ https://www.ncbi.nlm.nih.gov/pubmed/35917175 http://dx.doi.org/10.1172/jci.insight.159406 |
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