PMID- 37325657
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20240315
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Involvement of CD40-CD40L and ICOS-ICOSL in the development of chronic 
      rhinosinusitis by targeting eosinophils.
PG  - 1171308
LID - 10.3389/fimmu.2023.1171308 [doi]
LID - 1171308
AB  - BACKGROUND: Chronic rhinosinusitis (CRS), whose prevalence and pathogenesis are 
      age-related, is characterized by nasal tissue eosinophil infiltration. CD40-CD40 
      ligand (CD40L) pathway involves in the eosinophil-mediated inflammation, and 
      inducible co-stimulator (ICOS)-ICOS ligand (ICOSL) signal can strengthen 
      CD40-CD40L interaction. Whether CD40-CD40L and ICOS-ICOSL have a role in the 
      development of CRS remains unknown. OBJECTIVES: The aim of this study is to 
      investigate the association of CD40-CD40L and ICOS-ICOSL expression with CRS and 
      underlying mechanisms. METHODS: Immunohistology detected the expression of CD40, 
      CD40L, ICOS, and ICOSL. Immunofluorescence was performed to evaluate the 
      co-localizations of CD40 or ICOSL with eosinophils. Correlations between 
      CD40-CD40L and ICOS-ICOSL as well as clinical parameters were analyzed. Flow 
      cytometry was used to explore the activation of eosinophils by CD69 expression 
      and the CD40 and ICOSL expression on eosinophils. RESULTS: Compared with the 
      non-eCRS subset, ECRS (eosinophilic CRS) subset showed significantly increased 
      CD40, ICOS, and ICOSL expression. The CD40, CD40L, ICOS, and ICOSL expressions 
      were all positively correlated with eosinophil infiltration in nasal tissues. 
      CD40 and ICOSL were mainly expressed on eosinophils. ICOS expression was 
      significantly correlated with the expression of CD40-CD40L, whereas ICOSL 
      expression was correlated with CD40 expression. ICOS-ICOSL expression positively 
      correlated with blood eosinophils count and disease severity. rhCD40L and rhICOS 
      significantly enhanced the activation of eosinophils from patients with ECRS. 
      Tumor necrosis factor-alpha (TNF-alpha) and interleukin-5 (IL-5) obviously upregulated 
      CD40 expression on eosinophils, which was significantly inhibited by the p38 
      mitogen-activated protein kinase (MAPK) inhibitor. CONCLUSIONS: Increased 
      CD40-CD40L and ICOS-ICOSL expressions in nasal tissues are linked to eosinophils 
      infiltration and disease severity of CRS. CD40-CD40L and ICOS-ICOSL signals 
      enhance eosinophils activation of ECRS. TNF-alpha and IL-5 regulate eosinophils 
      function by increasing CD40 expression partly via p38 MAPK activation in patients 
      with CRS.
CI  - Copyright (c) 2023 Zhou, Shi, Fan, Zheng, Wang, Liu, Xie, Liu and Jiao.
FAU - Zhou, Aina
AU  - Zhou A
AD  - Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow 
      University, Suzhou, China.
FAU - Shi, Chenxi
AU  - Shi C
AD  - Department of Pathology, The First Affiliated Hospital of Soochow University, 
      Suzhou, China.
FAU - Fan, Yuhui
AU  - Fan Y
AD  - Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow 
      University, Suzhou, China.
FAU - Zheng, Yushuang
AU  - Zheng Y
AD  - Department of Pathology, The First Affiliated Hospital of Soochow University, 
      Suzhou, China.
FAU - Wang, Jue
AU  - Wang J
AD  - Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow 
      University, Suzhou, China.
FAU - Liu, Zhichen
AU  - Liu Z
AD  - Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow 
      University, Suzhou, China.
FAU - Xie, Huanxia
AU  - Xie H
AD  - Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow 
      University, Suzhou, China.
FAU - Liu, Jisheng
AU  - Liu J
AD  - Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow 
      University, Suzhou, China.
FAU - Jiao, Qingqing
AU  - Jiao Q
AD  - Department of Dermatology, The First Affiliated Hospital of Soochow University, 
      Suzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230601
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 147205-72-9 (CD40 Ligand)
RN  - 0 (Interleukin-5)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (CD40 Antigens)
RN  - 0 (Interleukin-2)
RN  - 0 (ICOS protein, human)
RN  - 0 (Inducible T-Cell Co-Stimulator Protein)
SB  - IM
MH  - Humans
MH  - *CD40 Ligand
MH  - Eosinophils/metabolism
MH  - Interleukin-5
MH  - Tumor Necrosis Factor-alpha
MH  - CD40 Antigens
MH  - *Eosinophilia/metabolism
MH  - Interleukin-2
MH  - Inducible T-Cell Co-Stimulator Protein
PMC - PMC10267736
OTO - NOTNLM
OT  - CD40-CD40L
OT  - ICOS-ICOSL
OT  - IL-5
OT  - TNF-alpha
OT  - chronic rhinosinusitis
OT  - eosinophils
OT  - p38 MAPK
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/06/16 06:42
MHDA- 2023/06/19 13:08
PMCR- 2023/01/01
CRDT- 2023/06/16 04:27
PHST- 2023/02/22 00:00 [received]
PHST- 2023/03/20 00:00 [accepted]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/06/16 06:42 [pubmed]
PHST- 2023/06/16 04:27 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1171308 [doi]
PST - epublish
SO  - Front Immunol. 2023 Jun 1;14:1171308. doi: 10.3389/fimmu.2023.1171308. 
      eCollection 2023.