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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
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.
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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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