Involvement of PD-1+CD4+ T cells in the development of traumatic tracheal stenosis by regulating the IL-17/STAT3 pathway.
Biochim Biophys Acta Mol Basis Dis
; 1870(6): 167216, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38718843
ABSTRACT
Studies have highlighted an upregulation of PD-1 expression in CD4+ T cells, which accelerates lung fibrosis by activating the IL-17/STAT3 pathway, leading to IL-17A and TGF-ß1 secretion. However, the relation with traumatic tracheal stenosis (TS) remains unexplored. Our analysis found significant increases in PD-1+CD4+ T cells, IL-17A, and TGF-ß1 in the TS patients (n = 10). The cellular model used CD4+ T cells co-cultured with bronchial fibroblasts while the animal model used a nylon brush to scrape the damaged tracheal mucosa. Interventions with PD-1 and STAT3 inhibitors both in vitro (n = 5) and in vivo (n = 6) showed decreased expression of TGF-ß1 and IL-17A in CD4+ T cells, decreased collagen I synthesis in vitro, and reduced tractal fibrosis in vivo. Furthermore, PD-1's modulation of the STAT3 was evident. This research unveils PD-1+CD4+ T cells' role in TS, thus suggesting a novel immunotherapeutic strategy to counteract tracheal fibrosis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estenose Traqueal
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Linfócitos T CD4-Positivos
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Transdução de Sinais
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Interleucina-17
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Fator de Transcrição STAT3
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Receptor de Morte Celular Programada 1
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article