Staff View: A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells

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

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...

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Main Authors:	Wojciech, Lukasz, Png, Chin Wen, Koh, Eileen Y, Kioh, Dorinda Yan Qin, Deng, Lei, Wang, Ziteng, Wu, Liang Zhe, Hamidinia, Maryam, Tung, Desmond Wh, Zhang, Wei, Pettersson, Sven *, Chan, Eric Chun Yong, Zhang, Yongliang, Tan, Kevin Sw, Gascoigne, Nicholas Rj
Format:	Article
Published:	EMBO Press 2023
Subjects:	QP Physiology QR Microbiology RC Internal medicine
Online Access:	http://eprints.sunway.edu.my/2754/ https://doi.org/10.15252/embj.2022112963
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id	my.sunway.eprints.2754
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spelling	my.sunway.eprints.27542024-07-08T02:55:47Z http://eprints.sunway.edu.my/2754/ A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells Wojciech, Lukasz Png, Chin Wen Koh, Eileen Y Kioh, Dorinda Yan Qin Deng, Lei Wang, Ziteng Wu, Liang Zhe Hamidinia, Maryam Tung, Desmond Wh Zhang, Wei Pettersson, Sven * Chan, Eric Chun Yong Zhang, Yongliang Tan, Kevin Sw Gascoigne, Nicholas Rj QP Physiology QR Microbiology RC Internal medicine 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. EMBO Press 2023 Article PeerReviewed 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 https://doi.org/10.15252/embj.2022112963 10.15252/embj.2022112963
institution	Sunway University
building	Sunway Campus Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Sunway University
content_source	Sunway Institutional Repository
url_provider	http://eprints.sunway.edu.my/
topic	QP Physiology QR Microbiology RC Internal medicine
spellingShingle	QP Physiology QR Microbiology RC Internal medicine Wojciech, Lukasz Png, Chin Wen Koh, Eileen Y Kioh, Dorinda Yan Qin Deng, Lei Wang, Ziteng Wu, Liang Zhe Hamidinia, Maryam Tung, Desmond Wh Zhang, Wei Pettersson, Sven * Chan, Eric Chun Yong Zhang, Yongliang Tan, Kevin Sw Gascoigne, Nicholas Rj A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells
description	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.
format	Article
author	Wojciech, Lukasz Png, Chin Wen Koh, Eileen Y Kioh, Dorinda Yan Qin Deng, Lei Wang, Ziteng Wu, Liang Zhe Hamidinia, Maryam Tung, Desmond Wh Zhang, Wei Pettersson, Sven * Chan, Eric Chun Yong Zhang, Yongliang Tan, Kevin Sw Gascoigne, Nicholas Rj
author_facet	Wojciech, Lukasz Png, Chin Wen Koh, Eileen Y Kioh, Dorinda Yan Qin Deng, Lei Wang, Ziteng Wu, Liang Zhe Hamidinia, Maryam Tung, Desmond Wh Zhang, Wei Pettersson, Sven * Chan, Eric Chun Yong Zhang, Yongliang Tan, Kevin Sw Gascoigne, Nicholas Rj
author_sort	Wojciech, Lukasz
title	A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells
title_short	A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells
title_full	A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells
title_fullStr	A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells
title_full_unstemmed	A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells
title_sort	tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory t cells
publisher	EMBO Press
publishDate	2023
url	http://eprints.sunway.edu.my/2754/ https://doi.org/10.15252/embj.2022112963
_version_	1804069667595091968
score	13.211869

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

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