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Cited by 266

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TLR4 regulates RORγt+ regulatory T-cell responses and susceptibility to colon inflammation through interaction with Akkermansia muciniphila

Open access
Liu, Yaojiang, Yang, Min, Tang, Li, Wang, Fengchao, Huang, Shengjie, Liu, Shuang, Lei, Yuanyuan, Wang, Sumin, Xie, Zhuo, Wang, Wei, Zhao, Xiaoyan, Tang, Bo, Yang, Shiming·2022·Microbiome

Abstract

Background: Well-balanced interactions between gut microbiota and the immune system are essential to prevent chronic intestinal inflammation, as observed in inflammatory bowel diseases (IBD). Toll-like receptor 4 (TLR4) functions as a sensor mediating the crosstalk between the intestinal commensal microbiome and host immunity, but the influence of TLR4 on the shaping of intestinal microbiota and immune responses during colon inflammation remains poorly characterized. We investigated whether the different susceptibilities to colitis between wild-type (WT) and TLR4−/− mice were gut microbiota-dependent and aimed to identify the potential immunity modulation mechanism. Methods: We performed antibiotic depletion of the microbiota, cohousing experiments, and faecal microbiota transplantation (FMT) in WT and TLR4−/− mice to assess the influence of TLR4 on intestinal microbial ecology. 16S rRNA sequencing was performed to dissect microbial discrepancies, and dysbiosis-associated immune perturbation was investigated by flow cytometry. Akkermansia muciniphila (A. muciniphila)-mediated immune modulation was confirmed through the T-cell transfer colitis model and bone marrow chimaera construction. Results: TLR4−/− mice experienced enhanced susceptibility to DSS-induced colitis. 16S rRNA sequencing showed notable discrepancy in the gut microbiota between WT and TLR4−/− mice. In particular, A. muciniphila contributed most to distinguishing the two groups. The T-cell transfer colitis model and bone marrow transplantation (BMT) consistently demonstrated that A. muciniphila ameliorated colitis by upregulating RORγt+ Treg cell-mediated immune responses. Mucosal biopsies from human manifested parallel outcomes with colon tissue from WT mice, as evidenced by the positive correlation between TLR4 expression and intestinal A. muciniphila colonization during homeostasis. Conclusions: Our results demonstrate a novel protective role of TLR4 against intestinal inflammation, wherein it can modulate A. muciniphila-associated immune responses. These findings provide a new perspective on host-commensal symbiosis, which may be beneficial for developing potential therapeutic strategies. Graphical Abstract:

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Metadata

Authors
Liu, Y., Yang, M., Tang, L., Wang, F., Huang, S., Liu, S., Lei, Y., Wang, S., Xie, Z., Wang, W., Zhao, X., Tang, B., & Yang, S.
Venue
Microbiome
Published
2022-06-27
Volume
10
Issue
1
Pages
98-98
ISSN
2049-2618 (ISSN-L)
OpenAlex
W4283582325
Cited by
266
References
66
FWCI
15.47
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: TLR4 regulates RORγt+ regulatory T-cell responses and susceptibility to colon inflammation through interaction with Akkermansia muciniphila. https://app.cochat.ai/papers/10.1186/s40168-022-01296-x
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Liu, Y., Yang, M., Tang, L., Wang, F., Huang, S., Liu, S., Lei, Y., Wang, S., Xie, Z., Wang, W., Zhao, X., Tang, B., & Yang, S. (2022). TLR4 regulates RORγt+ regulatory T-cell responses and susceptibility to colon inflammation through interaction with Akkermansia muciniphila. Microbiome. https://doi.org/10.1186/s40168-022-01296-x

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