Portal de investigação
Deregulated immune cell recruitment orchestrated by c-MET impairs pulmonary inflammation and fibrosis
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Barbosa-Matos, Catarina
- Borges-Pereira, Caroline
- Liborio-Ramos, Sofia
- Fernandes, Raquel
- Oliveira, Marcela
- Mendes-Frias, Ana
- Silvestre, Ricardo
- Osorio, Nuno S.
- Santos, Rita F.
- Guimaraes, Susana
- Mazzone, Massimiliano
- Carvalho, Agostinho
- Cunha, Cristina
Unidades de investigação
Abstract
Background Pulmonary fibrosis (PF) represents the pathologic end stage of several interstitial lung diseases (ILDs) associated with high morbidity and mortality rates. However, current treatments can only delay disease progression rather than provide a cure. The role of inflammation in PF progression is well-established, but new insights into immune regulation are fundamental for developing more efficient therapies. c-MET signaling has been implicated in the migratory capacity and effector functions of immune cells. Nevertheless, the role of this signaling pathway in the context of PF-associated lung diseases remains unexplored.Methods To determine the influence of c-MET in immune cells in the progression of pulmonary fibrosis, we used a conditional deletion of c-Met in immune cells. To induce pulmonary fibrosis mice were administered with bleomycin (BLM) intratracheally. Over the course of 21 days, mice were assessed for weight change, and after euthanasia at different timepoints, bronchoalveolar lavage fluid cells and lung tissue were assessed for inflammation and fibrosis. Furthermore, c-MET expression was assessed in cryobiopsy sections, bronchoalveolar lavage fluid cells samples and single cell RNA-sequencing dataset from human patients with distinct interstitial lung diseases.Results c-MET expression was induced in lung immune cells, specifically in T cells, interstitial macrophages, and neutrophils, during the inflammatory phase of BLM-induced PF mouse model. Deletion of c-Met in immune cells correlated with earlier weight recovery and improved survival of BLM-treated mice. Moreover, the deletion of c-Met in immune cells was associated with early recruitment of the immune cell populations, normally found to express c-MET, leading to a subsequent attenuation of the cytotoxic and proinflammatory environment. Consequently, the less extensive inflammatory response, possibly coupled with tissue repair, culminated in less exacerbated fibrotic lesions. Furthermore, c-MET expression was up-regulated in lung T cells from patients with fibrosing ILD, suggesting a potential involvement of c-MET in the development of fibrosing disease.Conclusions These results highlight the critical contribution of c-MET signaling in immune cells to their enhanced uncontrolled recruitment and activation toward a proinflammatory and profibrotic phenotype, leading to the exacerbation of lung injury and consequent development of fibrosis.
Dados da publicação
- ISSN/ISSNe:
- 1465-993X, 1465-9921
- Tipo:
- Article
- Páginas:
- -
- Link para outro recurso:
- www.scopus.com
Respiratory Research BioMed Central Ltd.
Citações Recebidas na Web of Science: 1
Citações Recebidas na Scopus: 1
Documentos
- Não há documentos
Filiações
Keywords
- Bleomycin; c-MET; ILDs; Inflammation; Pulmonary fibrosis
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Citar a publicação
Barbosa C,Borges C,Liborio S,Fernandes R,Oliveira M,Mendes A,Silvestre R,Osorio NS,Bastos HN,Santos RF,Guimaraes S,Morais A,Mazzone M,Carvalho A,Cunha C,Costa S. Deregulated immune cell recruitment orchestrated by c-MET impairs pulmonary inflammation and fibrosis. Respir. Res. 2024. 25. (1):257. IF:5,800. (1).
