PMID- 34178329
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220424
IS  - 2050-0068 (Print)
IS  - 2050-0068 (Electronic)
IS  - 2050-0068 (Linking)
VI  - 10
IP  - 6
DP  - 2021
TI  - IL-33/ST2 axis deficiency exacerbates neutrophil-dominant allergic airway 
      inflammation.
PG  - e1300
LID - 10.1002/cti2.1300 [doi]
LID - e1300
AB  - OBJECTIVE: The IL-33/ST2 axis has been extensively investigated in type 2 
      eosinophilic inflammation. Here, we aimed to investigate the role of the 
      IL-33/ST2 axis in neutrophil-dominant allergic airway inflammation. METHODS: 
      House-dust mite (HDM) extract and lipopolysaccharide (LPS) were administered to 
      establish a murine model of neutrophil-dominant allergic airway inflammation. The 
      formation of neutrophilic extracellular traps (NETs) in the lung tissues was 
      demonstrated by immunofluorescence imaging. Mature IL-33 in bronchoalveolar 
      lavage fluid (BALF) was detected by Western blotting. The neutrophilic chemokine 
      KC produced by bone marrow-derived macrophages (BMDMs) or primary alveolar 
      epithelial cells was measured with a commercial ELISA kit. RESULTS: In the 
      present study, we observed neutrophilic inflammation and tight junction damage in 
      the lungs of mice sensitised with HDM and LPS. Furthermore, sensitisation with 
      HDM and LPS resulted in the formation of NETs, accompanied by increased levels of 
      mature IL-33 in the BALF. Moreover, LPS damaged the epithelial tight junction 
      protein occludin directly or indirectly by inducing NET formation. Surprisingly, 
      IL-33 deficiency augmented neutrophilia and epithelial barrier injury in the 
      lungs of mice after sensitisation with HDM and LPS. Similarly, the absence of ST2 
      exacerbated the neutrophilic inflammatory response, decreased the expression of 
      occludin and exacerbated the severity of neutrophil-dominant allergic airway 
      inflammation in an HDM/LPS-induced mouse model. Mechanistically, BMDMs and 
      alveolar epithelial cells from IL-33- or ST2-deficient mice tended to produce 
      higher levels of the neutrophilic chemokine KC. CONCLUSIONS: These results 
      demonstrated that the IL-33/ST2 axis may play a protective role in 
      neutrophil-dominant allergic airway inflammation.
CI  - (c) 2021 The Authors. Clinical & Translational Immunology published by John Wiley & 
      Sons Australia, Ltd on behalf of Australian and New Zealand Society for 
      Immunology, Inc.
FAU - Ma, Qiyun
AU  - Ma Q
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Qian, Yan
AU  - Qian Y
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Jiang, Jingxian
AU  - Jiang J
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Wu, Jingjing
AU  - Wu J
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Song, Meijuan
AU  - Song M
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Li, Xinyu
AU  - Li X
AD  - NHC Key Laboratory of Antibody Technique Jiangsu Key Laboratory of Pathogen 
      Biology Department of Immunology Nanjing Medical University Nanjing China.
FAU - Chen, Zhongqi
AU  - Chen Z
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Wang, Zhengxia
AU  - Wang Z
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Zhu, Ranran
AU  - Zhu R
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Sun, Zhixiao
AU  - Sun Z
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Huang, Mao
AU  - Huang M
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Ji, Ningfei
AU  - Ji N
AD  - Department of Respiratory and Critical Care Medicine The First Affiliated 
      Hospital of Nanjing Medical University Nanjing China.
FAU - Zhang, Mingshun
AU  - Zhang M
AUID- ORCID: 0000-0001-5925-0168
AD  - NHC Key Laboratory of Antibody Technique Jiangsu Key Laboratory of Pathogen 
      Biology Department of Immunology Nanjing Medical University Nanjing China.
LA  - eng
PT  - Journal Article
DEP - 20210616
PL  - Australia
TA  - Clin Transl Immunology
JT  - Clinical & translational immunology
JID - 101638268
PMC - PMC8207976
OTO - NOTNLM
OT  - animal models
OT  - asthma
OT  - barrier
OT  - epithelium
OT  - inflammation
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/29 06:00
MHDA- 2021/06/29 06:01
PMCR- 2021/06/16
CRDT- 2021/06/28 06:00
PHST- 2020/09/15 00:00 [received]
PHST- 2021/04/30 00:00 [revised]
PHST- 2021/05/27 00:00 [revised]
PHST- 2021/05/27 00:00 [accepted]
PHST- 2021/06/28 06:00 [entrez]
PHST- 2021/06/29 06:00 [pubmed]
PHST- 2021/06/29 06:01 [medline]
PHST- 2021/06/16 00:00 [pmc-release]
AID - CTI21300 [pii]
AID - 10.1002/cti2.1300 [doi]
PST - epublish
SO  - Clin Transl Immunology. 2021 Jun 16;10(6):e1300. doi: 10.1002/cti2.1300. 
      eCollection 2021.