Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation - Sorbonne Université
Journal Articles JCI Insight Year : 2022

Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation

Otriv Nguekap Tchoumba
  • Function : Author
Gabriel Pires
  • Function : Author
Sarah Dandou
  • Function : Author
Julien Campagne
  • Function : Author
Guillaume Churlaud
  • Function : Author
Gwladys Fourcade
  • Function : Author
Thomas W Hoffmann
  • Function : Author
  • PersonId : 1221765
Francesco Strozzi
  • Function : Author
Camille Gaal
  • Function : Author
Christophe Bonny
  • Function : Author
Emmanuelle Le Chatelier
  • Function : Author
Stanislav Dusko Erlich
  • Function : Author
Harry Sokol
David Klatzmann

Abstract

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.

Domains

Immunology
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Dates and versions

hal-03797609 , version 1 (04-10-2022)

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Nicolas Tchitchek, Otriv Nguekap Tchoumba, Gabriel Pires, Sarah Dandou, Julien Campagne, et al.. Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation. JCI Insight, 2022, 7 (17), ⟨10.1172/jci.insight.159406⟩. ⟨hal-03797609⟩
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