Hedgehog signaling pathway regulates Th17 cell differentiation in asthma via IL-6/STAT3 signaling.
Int Immunopharmacol
; 139: 112771, 2024 Sep 30.
Article
en En
| MEDLINE
| ID: mdl-39074418
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Asma
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Transducción de Señal
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Diferenciación Celular
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Interleucina-6
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Factor de Transcripción STAT3
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Proteínas Hedgehog
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Células Th17
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Proteína Gli3 con Dedos de Zinc
Límite:
Animals
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Child
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Female
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Humans
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Male
Idioma:
En
Año:
2024
Tipo del documento:
Article