Direct activation of toll-like receptor 4 signaling in group 2 innate lymphoid cells contributes to inflammatory responses of allergic diseases

Group 2 innate lymphoid cells (ILC2s) are key players in type 2 immunity, but whether they can be directly activated by microbial ligands remain uncertain. In this study, we observed a positive correlation between blood endotoxin (LPS) levels and circulating ILC2s in allergic patients. <i>In vitro</i>, LPS robustly induced ILC2 proliferation and production of type 2 effector cytokines. RNA-seq revealed a type 2 immune-responsive profile in LPS-stimulated ILC2s. Notably, ILC2s lost their LPS-mediated growth and activation capacity when treated with TLR4 receptor antagonists and inhibitors of the NF-κB and JAK pathways, though this effect was not observed with IL-33 receptor blocking antibodies. Genetically, ILC2s from TLR4 knockout (KO) mice, but not from ST2 KO mice, were unresponsive to LPS. Collectively, these findings suggest a direct, non-canonical activation mechanism of ILC2s via the LPS-TLR4-NF-κB/JAK signaling axis.

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Publication Details

Journal
iScience
Published
2024-10-23
DOI
https://doi.org/10.1016/j.isci.2024.111240
Citations
4
Primary Topic
IL-33, ST2, and ILC Pathways
Type
article
Field-Weighted Citation Impact
0.96

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article

Direct activation of toll-like receptor 4 signaling in group 2 innate lymphoid cells contributes to inflammatory responses of allergic diseases

Li She, Yuzhang Gao, Kexin Mo, Na Xiong et al.
4 citations
iScience
IL-33, ST2, and ILC Pathways
0.96
article

Direct activation of toll-like receptor 4 signaling in group 2 innate lymphoid cells contributes to inflammatory responses of allergic diseases

Li She, Yuzhang Gao, Kexin Mo, Na Xiong, Shuting Guo, Hong Zan, Hamad H. Alanazi, Weihong Jiang, Zhihai Xie, Xin Zhang, Qing-quan Xiong, Daniel P. Chupp, Zhenming Xu, Yilun Sun, Jingwei Wang, Xiao-Dong Li, Nu Zhang, Yong Liu, Yimin Xu, Hui Jiang, Yuxuan Yu
article en
4 citations

Abstract

Group 2 innate lymphoid cells (ILC2s) are key players in type 2 immunity, but whether they can be directly activated by microbial ligands remain uncertain. In this study, we observed a positive correlation between blood endotoxin (LPS) levels and circulating ILC2s in allergic patients. <i>In vitro</i>, LPS robustly induced ILC2 proliferation and production of type 2 effector cytokines. RNA-seq revealed a type 2 immune-responsive profile in LPS-stimulated ILC2s. Notably, ILC2s lost their LPS-mediated growth and activation capacity when treated with TLR4 receptor antagonists and inhibitors of the NF-κB and JAK pathways, though this effect was not observed with IL-33 receptor blocking antibodies. Genetically, ILC2s from TLR4 knockout (KO) mice, but not from ST2 KO mice, were unresponsive to LPS. Collectively, these findings suggest a direct, non-canonical activation mechanism of ILC2s via the LPS-TLR4-NF-κB/JAK signaling axis.

iScienceVol. 27(11)
Central South University (CN), The University of Texas at San Antonio Health Science Center (US), Umm al-Qura University (SA), National Clinical Research (US), Guangzhou Medical University (CN)
Max and Minnie Tomerlin Voelcker Fund, Guangzhou Medical University, National Natural Science Foundation of China, China Postdoctoral Science Foundation, Xiangya Hospital, Central South University, National Key Research and Development Program of China
Good health and well-being
Openalex Percentile: Top 24%
IL-33, ST2, and ILC Pathways
0.96
DOIOpen Access PDFOpenAlex
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