iScience (Nov 2024)
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 Liu,
- Xiao-Dong Li
Affiliations
- Li She
- Department of Otolaryngology-Head and Neck Surgery, Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders, Otolaryngology Major Disease Research Key Laboratory of Hunan Province, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
- Hamad H. Alanazi
- Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences at Al-Qurayyat, Jouf University, Aldwally Road, Al-Qurayyat 77454, Saudi Arabia
- Yimin Xu
- Department of Otolaryngology-Head and Neck Surgery, Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders, Otolaryngology Major Disease Research Key Laboratory of Hunan Province, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
- Yuxuan Yu
- Department of Otolaryngology-Head and Neck Surgery, Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders, Otolaryngology Major Disease Research Key Laboratory of Hunan Province, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
- Yuzhang Gao
- Department of Otolaryngology-Head and Neck Surgery, Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders, Otolaryngology Major Disease Research Key Laboratory of Hunan Province, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
- Shuting Guo
- Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, 1 Xinzao Road, Guangzhou, Guangdong 511495, China
- Qingquan Xiong
- Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, 1 Xinzao Road, Guangzhou, Guangdong 511495, China
- Hui Jiang
- Department of Gynecology, The Fifth Affiliated Hospital, Guangzhou Medical University, 621 Gangwan Road, Guangzhou, Guangdong 510700, China
- Kexin Mo
- Department of Gynecology, The Fifth Affiliated Hospital, Guangzhou Medical University, 621 Gangwan Road, Guangzhou, Guangdong 510700, China
- Jingwei Wang
- Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
- Daniel P. Chupp
- Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
- Hong Zan
- Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
- Zhenming Xu
- Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
- Yilun Sun
- Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
- Na Xiong
- Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
- Nu Zhang
- Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
- Zhihai Xie
- Department of Otolaryngology-Head and Neck Surgery, Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders, Otolaryngology Major Disease Research Key Laboratory of Hunan Province, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
- Weihong Jiang
- Department of Otolaryngology-Head and Neck Surgery, Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders, Otolaryngology Major Disease Research Key Laboratory of Hunan Province, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
- Xin Zhang
- Department of Otolaryngology-Head and Neck Surgery, Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders, Otolaryngology Major Disease Research Key Laboratory of Hunan Province, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
- Yong Liu
- Department of Otolaryngology-Head and Neck Surgery, Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders, Otolaryngology Major Disease Research Key Laboratory of Hunan Province, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; Corresponding author
- Xiao-Dong Li
- Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA; Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, 1 Xinzao Road, Guangzhou, Guangdong 511495, China; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 11
p. 111240
Abstract
Summary: 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.
