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

Li She, Hamad H. Alanazi, Yimin Xu, Yuxuan Yu, Yuzhang Gao, Shuting Guo, Qingquan Xiong, Hui Jiang, Kexin Mo, Jingwei Wang, Daniel P. Chupp, Hong Zan, Zhenming Xu, Yilun Sun, Na Xiong, Nu Zhang, Zhihai Xie, Weihong Jiang, Xin Zhang, Yong LiuXiao Dong Li

Research output: Contribution to journalArticlepeer-review

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. In vitro, 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.

Original languageEnglish (US)
Article number111240
JournaliScience
Volume27
Issue number11
DOIs
StatePublished - Nov 15 2024
Externally publishedYes

Keywords

  • Cell biology
  • Immunology
  • Pathophysiology

ASJC Scopus subject areas

  • General

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