학술논문
The transcription factor XBP1 in dendritic cells promotes the T H 2 cell response in airway allergy.
Document Type
Academic Journal
Author
Yang G; Department of Otolaryngology, Head and Neck Surgery, Longgang Central Hospital, Shenzhen, China.; Zeng XH; Longgang ENT Hospital, Shenzhen, China.; Shenzhen ENT Institute, Shenzhen, China.; Geng XR; Longgang ENT Hospital, Shenzhen, China.; Shenzhen ENT Institute, Shenzhen, China.; Liu JQ; Longgang ENT Hospital, Shenzhen, China.; Shenzhen ENT Institute, Shenzhen, China.; Mo LH; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China.; Institute of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China.; Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.; Luo XQ; Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.; Liu HZ; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China.; Institute of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China.; Zhang YY; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China.; Institute of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China.; Yang LT; Department of General Practice Medicine and Respirology, Third Affiliated Hospital, Shenzhen University School of Medicine, Shenzhen, China.; Huang QM; Department of General Practice Medicine and Respirology, Third Affiliated Hospital, Shenzhen University School of Medicine, Shenzhen, China.; Xiao XJ; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China.; Institute of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China.; Liu J; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China.; Institute of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China.; Xu LZ; Department of Immunology, Weifang Medical University, Weifang, China.; Liu DB; Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.; Liu XY; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China.; Institute of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China.; Liu ZQ; Longgang ENT Hospital, Shenzhen, China.; Shenzhen ENT Institute, Shenzhen, China.; Yang PC; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China.; Institute of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China.
Source
Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101465400 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1937-9145 (Electronic) Linking ISSN: 19450877 NLM ISO Abbreviation: Sci Signal Subsets: MEDLINE
Subject
Language
English
Abstract
Dendritic cells (DCs) that express T cell immunoglobulin domain molecule-4 (TIM4), a cell surface receptor for phosphatidylserine, induce T helper 2 (T H 2) cell responses and allergic reactions. We elucidated the role of the transcription factor X-box-binding protein-1 (XBP1) in the induction of the T H 2 cell response through its role in generating TIM4 + DCs. We found that XBP1 was required for TIM4 mRNA and protein expression in airway DCs in response to the cytokine interleukin-2 (IL-2) and that this pathway was required for TIM4 expression on DCs in response to the allergens PM2.5 and Derf1. The IL-2-XBP1-TIM4 axis in DCs contributed to Derf1/PM2.5-induced, aberrant T H 2 cell responses in vivo. An interaction between the guanine nucleotide exchange factor Son of sevenless-1 (SOS1) and the GTPase RAS promoted XBP1 and TIM4 production in DCs. Targeting the XBP1-TIM4 pathway in DCs prevented or alleviated experimental airway allergy. Together, these data suggest that XBP1 is required for T H 2 cell responses by inducing the development of TIM4 + DCs, which depends on the IL-2-XBP1-SOS1 axis. This signaling pathway provides potential therapeutic targets for the treatment of T H 2 cell-dependent inflammation or allergic diseases.