PMID- 37368951
OWN - NLM
STAT- MEDLINE
DCOM- 20230629
LR  - 20230629
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 16
IP  - 791
DP  - 2023 Jun 27
TI  - The transcription factor XBP1 in dendritic cells promotes the T(H)2 cell response 
      in airway allergy.
PG  - eabm9454
LID - 10.1126/scisignal.abm9454 [doi]
AB  - 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.
FAU - Yang, Gui
AU  - Yang G
AUID- ORCID: 0000-0002-5413-0121
AD  - Department of Otolaryngology, Head and Neck Surgery, Longgang Central Hospital, 
      Shenzhen, China.
FAU - Zeng, Xian-Hai
AU  - Zeng XH
AUID- ORCID: 0009-0000-3067-3378
AD  - Longgang ENT Hospital, Shenzhen, China.
AD  - Shenzhen ENT Institute, Shenzhen, China.
FAU - Geng, Xiao-Rui
AU  - Geng XR
AUID- ORCID: 0000-0002-9912-6687
AD  - Longgang ENT Hospital, Shenzhen, China.
AD  - Shenzhen ENT Institute, Shenzhen, China.
FAU - Liu, Jiang-Qi
AU  - Liu JQ
AUID- ORCID: 0009-0007-9143-7708
AD  - Longgang ENT Hospital, Shenzhen, China.
AD  - Shenzhen ENT Institute, Shenzhen, China.
FAU - Mo, Li-Hua
AU  - Mo LH
AUID- ORCID: 0000-0003-4048-3935
AD  - Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, 
      China.
AD  - Institute of Allergy and Immunology, Shenzhen University School of Medicine and 
      State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen 
      University, Shenzhen, China.
AD  - Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical 
      University, Shenzhen, China.
FAU - Luo, Xiang-Qian
AU  - Luo XQ
AUID- ORCID: 0000-0001-5132-0512
AD  - Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical 
      University, Shenzhen, China.
FAU - Liu, Hua-Zhen
AU  - Liu HZ
AUID- ORCID: 0000-0003-2311-6703
AD  - Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, 
      China.
AD  - Institute of Allergy and Immunology, Shenzhen University School of Medicine and 
      State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen 
      University, Shenzhen, China.
FAU - Zhang, Yuan-Yi
AU  - Zhang YY
AUID- ORCID: 0000-0003-2723-1477
AD  - Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, 
      China.
AD  - Institute of Allergy and Immunology, Shenzhen University School of Medicine and 
      State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen 
      University, Shenzhen, China.
FAU - Yang, Li-Teng
AU  - Yang LT
AUID- ORCID: 0009-0009-4784-8993
AD  - Department of General Practice Medicine and Respirology, Third Affiliated 
      Hospital, Shenzhen University School of Medicine, Shenzhen, China.
FAU - Huang, Qin-Miao
AU  - Huang QM
AUID- ORCID: 0009-0009-3439-1680
AD  - Department of General Practice Medicine and Respirology, Third Affiliated 
      Hospital, Shenzhen University School of Medicine, Shenzhen, China.
FAU - Xiao, Xiao-Jun
AU  - Xiao XJ
AUID- ORCID: 0009-0004-2003-7529
AD  - Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, 
      China.
AD  - Institute of Allergy and Immunology, Shenzhen University School of Medicine and 
      State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen 
      University, Shenzhen, China.
FAU - Liu, Jie
AU  - Liu J
AUID- ORCID: 0009-0006-7146-0102
AD  - Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, 
      China.
AD  - Institute of Allergy and Immunology, Shenzhen University School of Medicine and 
      State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen 
      University, Shenzhen, China.
FAU - Xu, Ling-Zhi
AU  - Xu LZ
AUID- ORCID: 0009-0004-5888-1135
AD  - Department of Immunology, Weifang Medical University, Weifang, China.
FAU - Liu, Da-Bo
AU  - Liu DB
AUID- ORCID: 0000-0001-7504-2668
AD  - Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical 
      University, Shenzhen, China.
FAU - Liu, Xiao-Yu
AU  - Liu XY
AUID- ORCID: 0000-0002-4158-8475
AD  - Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, 
      China.
AD  - Institute of Allergy and Immunology, Shenzhen University School of Medicine and 
      State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen 
      University, Shenzhen, China.
FAU - Liu, Zhi-Qiang
AU  - Liu ZQ
AUID- ORCID: 0000-0002-7353-8827
AD  - Longgang ENT Hospital, Shenzhen, China.
AD  - Shenzhen ENT Institute, Shenzhen, China.
FAU - Yang, Ping-Chang
AU  - Yang PC
AUID- ORCID: 0000-0002-6806-9464
AD  - Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, 
      China.
AD  - Institute of Allergy and Immunology, Shenzhen University School of Medicine and 
      State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen 
      University, Shenzhen, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230627
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Interleukin-2)
RN  - 0 (Transcription Factors)
RN  - 0 (Membrane Proteins)
RN  - 0 (Particulate Matter)
RN  - 0 (XBP1 protein, human)
RN  - 0 (X-Box Binding Protein 1)
SB  - IM
MH  - Humans
MH  - *Interleukin-2/metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Th2 Cells
MH  - Membrane Proteins/genetics/metabolism
MH  - *Hypersensitivity/genetics/metabolism
MH  - Dendritic Cells/metabolism
MH  - Particulate Matter/metabolism
MH  - X-Box Binding Protein 1/genetics
EDAT- 2023/06/27 19:13
MHDA- 2023/06/29 06:43
CRDT- 2023/06/27 14:02
PHST- 2023/06/29 06:43 [medline]
PHST- 2023/06/27 19:13 [pubmed]
PHST- 2023/06/27 14:02 [entrez]
AID - 10.1126/scisignal.abm9454 [doi]
PST - ppublish
SO  - Sci Signal. 2023 Jun 27;16(791):eabm9454. doi: 10.1126/scisignal.abm9454. Epub 
      2023 Jun 27.