PMID- 38403085
OWN - NLM
STAT- Publisher
LR  - 20240501
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Linking)
DP  - 2024 Feb 24
TI  - Epithelium-derived kallistatin promotes CD4(+) T-cell chemotaxis to T(H)2-type 
      inflammation in chronic rhinosinusitis.
LID - S0091-6749(24)00193-3 [pii]
LID - 10.1016/j.jaci.2024.02.013 [doi]
AB  - BACKGROUND: The function of kallistatin in airway inflammation, particularly 
      chronic rhinosinusitis with nasal polyps (CRSwNP), has not been elucidated. 
      OBJECTIVE: We sought to investigate the role of kallistatin in airway 
      inflammation. METHODS: Kallistatin and proinflammatory cytokine expression levels 
      were detected in nasal polyps. For the in vivo studies, we constructed the 
      kallistatin-overexpressing transgenic mice to elucidate the role of kallistatin 
      in airway inflammation. Furthermore, the levels of plasma IgE and proinflammatory 
      cytokines in the airways were evaluated in the kallistatin(-/-) rat in vivo model 
      under a type 2 inflammatory background. Finally, the Notch signaling pathway was 
      explored to understand the role of kallistatin in CRSwNP. RESULTS: We showed that 
      the expression of kallistatin was significantly higher in nasal polyps than in 
      the normal nasal mucosa and correlated with IL-4 expression. We also discovered 
      that the nasal mucosa of kallistatin-overexpressing transgenic mice expressed 
      higher levels of IL-4 expression, associating to T(H)2-type inflammation. 
      Interestingly, we observed lower IL-4 levels in the nasal mucosa and lower total 
      plasma IgE of the kallistatin(-/-) group treated with house dust mite allergen 
      compared with the wild-type house dust mite group. Finally, we observed a 
      significant increase in the expression of Jagged2 in the nasal epithelium cells 
      transduced with adenovirus-kallistatin. This heightened expression correlated 
      with increased secretion of IL-4, attributed to the augmented population of 
      CD4(+)CD45(+)Notch1(+) T cells. These findings collectively may contribute to the 
      induction of T(H)2-type inflammation. CONCLUSIONS: Kallistatin was demonstrated 
      to be involved in the CRSwNP pathogenesis by enhancing the T(H)2 inflammation, 
      which was found to be associated with more expression of IL-4, potentially 
      facilitated through Jagged2-Notch1 signaling in CD4(+) T cells.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Jiang, Lijie
AU  - Jiang L
AD  - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China; Department of Otorhinolaryngology, Nanfang 
      Hospital, Southern Medical University, Guangzhou, China.
FAU - Tang, Haocheng
AU  - Tang H
AD  - Department of Otorhinolaryngology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Lin, Tengjiao
AU  - Lin T
AD  - Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou 
      University of Chinese Medicine, Guangzhou, China.
FAU - Jiang, Yifeng
AU  - Jiang Y
AD  - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Li, Yanmei
AU  - Li Y
AD  - Basic and Clinical Medicine Teaching Laboratory, School of Medicine, Sun Yat-sen 
      University, Shenzhen, China.
FAU - Gao, Wenxiang
AU  - Gao W
AD  - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Deng, Jie
AU  - Deng J
AD  - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Huang, Zhaoqi
AU  - Huang Z
AD  - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Chen, Chuxin
AU  - Chen C
AD  - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Shi, Jianbo
AU  - Shi J
AD  - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China. Electronic address: tsjbent@163.com.
FAU - Zhou, Ti
AU  - Zhou T
AD  - Department of Biochemistry and Molecular Biology, Zhongshan School of Medicine, 
      Sun Yat-sen University, Guangzhou, China; China Key Laboratory of Tropical 
      Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 
      China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China. 
      Electronic address: zhouti2@mail.sysu.edu.cn.
FAU - Lai, Yinyan
AU  - Lai Y
AD  - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China. Electronic address: laiyy3@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240224
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
SB  - IM
OTO - NOTNLM
OT  - Kallistatin
OT  - Notch
OT  - T(H)2-type inflammation
OT  - chronic rhinosinusitis with nasal polyps (CRSwNP)
EDAT- 2024/02/26 00:42
MHDA- 2024/02/26 00:42
CRDT- 2024/02/25 19:15
PHST- 2023/03/31 00:00 [received]
PHST- 2023/12/23 00:00 [revised]
PHST- 2024/02/06 00:00 [accepted]
PHST- 2024/02/26 00:42 [pubmed]
PHST- 2024/02/26 00:42 [medline]
PHST- 2024/02/25 19:15 [entrez]
AID - S0091-6749(24)00193-3 [pii]
AID - 10.1016/j.jaci.2024.02.013 [doi]
PST - aheadofprint
SO  - J Allergy Clin Immunol. 2024 Feb 24:S0091-6749(24)00193-3. doi: 
      10.1016/j.jaci.2024.02.013.