Wojciech, Lukasz and Png, Chin Wen and Koh, Eileen Y and Kioh, Dorinda Yan Qin and Deng, Lei and Wang, Ziteng and Wu, Liang Zhe and Hamidinia, Maryam and Tung, Desmond Wh and Zhang, Wei and Pettersson, Sven * and Chan, Eric Chun Yong and Zhang, Yongliang and Tan, Kevin Sw and Gascoigne, Nicholas Rj (2023) A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells. The EMBO Journal, 42 (21). ISSN 1460-2075
Full text not available from this repository.Abstract
The large intestine harbors microorganisms playing unique roles in host physiology. The 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 in the large intestine after infection with the protist Blastocystis ST7 in a mouse model are associated with reduction of anti-inflammatory Treg cells and simultaneous expansion of pro-inflammatory Th17 responders. These alterations in CD4+ T cells depended on the tryptophan metabolite indole-3-acetaldehyde (I3AA) produced by this single-cell eukaryote. I3AA reduced the Treg subset in vivo and iTreg development in vitro by modifying their sensing of TGFβ, concomitantly affecting recognition of self-flora antigens by conventional CD4+ T cells. Parasite-derived I3AA also induces over-exuberant TCR signaling, manifested by increased CD69 expression and downregulation of co-inhibitor PD-1. We have thus identified a new mechanism dictating CD4+ fate decisions. The findings thus shine a new light on the ability of the protist microbiome and tryptophan metabolites, derived from them or other sources, to modulate the adaptive immune compartment, particularly in the context of gut inflammatory disorders.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | aryl hydrocarbon receptor; colitis; microbiome; regulatory T cells; tryptophan metabolites; |
| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RC Internal medicine |
| Divisions: | Others > Non Sunway Academics Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Department of Medical Sciences |
| Depositing User: | Ms Yong Yee Chan |
| Date Deposited: | 08 Jul 2024 02:55 |
| Last Modified: | 08 Jul 2024 02:55 |
| URI: | http://eprints.sunway.edu.my/id/eprint/2754 |
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