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Inhibition of IL-22-producing cells by Sutterella sp. bacteria

Dupraz, L.; Orianne, G.; Da Costa, G.; Gauthier, R.; Blondeau, A.; Boinet, M.; Creusot, L.; Magniez, A.; Chollet, L.; Rolhion, N.; Danne, C.; Dvorak, Z.; Seksik, P.; Sokol, H.; Michel, M.-L.

2025-03-22 immunology
10.1101/2025.03.20.644103 bioRxiv
Show abstract

The gut microbiota constitutes a complex ecosystem essential for host defense against infection and maturation of the immune system. Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohns disease, are characterized by a severe inflammation of the intestine, arising from dysregulated control of host-microbiota crosstalk. However, neither the genetic bases of IBD nor the immune responses involved are fully understood. The pathobionts are currently under investigation for their active role in the development and the severity of IBD. These bacteria are present in the microbiota of healthy individuals without causing disease but have pathogenic potential when the intestinal environment is disturbed. Here, we highlighted Sutterella sp. as a new commensal pathobiont for its capacity to modulate the host immune functions. This anaerobic Gram-negative bacterium inhibits IL-22 production and AhR activity in mice and humans. The effectors responsible for the biological activity are large (>30 kDa) protein-based compounds secreted by Sutterella sp. These data enhance our understanding of the mechanisms that regulate host immune functions and pave the way for new therapeutic strategies to control gut inflammation.

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