Hedgehog signaling pathway regulates Th17 cell differentiation in asthma via IL-6/STAT3 signaling.

Autor: Jin Y; Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, China; Department of Pediatrics, The First Affiliated Hospital of Shandong First Medical University, Jinan, China., Pan Z; Department of Respiration, Wuxi Children's Hospital, Wuxi, China., Zhou J; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China., Wang K; Department of Pediatrics, The First Affiliated Hospital of Shandong First Medical University, Jinan, China., Zhu P; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China., Wang Y; Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, China., Xu X; Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, China., Zhang J; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. Electronic address: j_pzhang@suda.edu.cn., Hao C; Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, China. Electronic address: hcl_md@sina.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Sep 30; Vol. 139, pp. 112771. Date of Electronic Publication: 2024 Jul 28.
DOI: 10.1016/j.intimp.2024.112771
Abstrakt: Asthma is the most prevalent chronic inflammatory disease of the airways in children. The most prevalent phenotype of asthma is eosinophilic asthma, which is driven by a Th2 immune response and can be effectively managed by inhaled corticosteroid therapy. However, there are phenotypes of asthma with Th17 immune response that are insensitive to corticosteroid therapy and manifest a more severe phenotype. The treatment of this corticosteroid-insensitive asthma is currently immature and requires further attention. The objective of this study is to elucidate the regulation of the Hedgehog signaling pathway in Th17 cell differentiation in asthma. The study demonstrated that both Smo and Gli3, key components of the Hedgehog signaling pathway, were upregulated in Th17 polarization in vitro and in a Th17-dominant asthma model in vivo. Inhibiting Smo with a small molecule inhibitor or genetically knocking down Gli3 was found to suppress Th17 polarization. Smo was found to increase in Th1, Th2, Th17 and Treg polarization, while Gli3 specifically increased in Th17 polarization. ChIP-qPCR analyses indicated that Gli3 can directly interact with IL-6 in T cells, inducing STAT3 phosphorylation and promoting Th17 cell differentiation. Furthermore, the study demonstrated a correlation between elevated Gli3 expression and IL-17A and IL-6 expression in children with asthma. In conclusion, the study demonstrated that the Hedgehog signaling pathway plays an important role in the pathogenesis of asthma, as it regulates the differentiation of Th17 cells through the IL-6/STAT3 signaling. This may provide a potential therapeutic target for corticosteroid-insensitive asthma driven by Th17 cells.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: