A tryptophan metabolite made by a gut microbiome eukaryote induces pro‐inflammatory T cells

• DOI: 10.15252/embj.2022112963
• Publication Date: 2023-09-25T07:16:10Z
• Authors: Lukasz Wojciech; Chin Wen Png; Eileen Y Koh; Dorinda Yan Qin Kioh; Lei Deng; Ziteng Wang; Liang‐zhe Wu; Maryam Hamidinia; Desmond WH Tung; Wei Zhang; Sven Pettersson; Eric Chun Yong Chan; Yongliang Zhang; Kevin SW Tan; Nicholas RJ Gasco...
• Keywords: Mice; Microbiota; Tryptophan; Animals; Eukaryota; Articles; T-Lymphocytes, Regulatory; Gastrointestinal Microbiome

Abstract The large intestine harbors microorganisms playing unique roles in host physiology. beneficial or detrimental outcome of host‐microbiome coexistence depends largely on the balance between regulators and responder intestinal CD4 + T cells. We found that ulcerative colitis‐like changes after infection with protist Blastocystis ST7 a mouse model are associated reduction anti‐inflammatory Treg cells simultaneous expansion pro‐inflammatory Th17 responders. These alterations depended tryptophan metabolite indole‐3‐acetaldehyde (I3AA) produced by this single‐cell eukaryote. I3AA reduced subset vivo iTreg development vitro modifying their sensing TGFβ, concomitantly affecting recognition self‐flora antigens conventional Parasite‐derived also induces over‐exuberant TCR signaling, manifested increased CD69 expression downregulation co‐inhibitor PD‐1. have thus identified new mechanism dictating fate decisions. findings shine light ability microbiome metabolites, derived from them other sources, to modulate adaptive immune compartment, particularly context gut inflammatory disorders.