Full-length IL-33 augments pulmonary fibrosis in an ST2- and Th2-independent, non-transcriptomic fashion.
Cell Immunol
; 383: 104657, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36603504
ABSTRACT
Mature IL-33 (MIL33) acting through its receptor, ST2, is known to regulate fibrosis. The precursor, full-length IL-33 (FLIL33), may function differently from MIL33 and independently of ST2. Here we report that genetic deletion of either IL-33 or ST2 attenuates pulmonary fibrosis in the bleomycin model, as does Cre-induced IL-33 deficiency in response to either acute or chronic bleomycin challenge. However, adenovirus-mediated gene delivery of FLIL33, but not MIL33, to the lungs of either wild-type or ST2-deficient mice potentiates the profibrotic effect of bleomycin without inducing a Th2 phenotype. In cultured mouse lung cells, FLIL33 overexpression induces moderate and distinct transcriptomic changes compared with a robust response induced by MIL33, whereas ST2 deletion abrogates the effects of both IL-33 forms. Thus, FLIL33 may contribute to fibrosis in an ST2-independent, Th2-independent, non-transcriptomic fashion, suggesting that pharmacological targeting of both FLIL33 and MIL33 may prove efficacious in patients with pulmonary fibrosis.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
Limite:
Animals
Idioma:
En
Revista:
Cell Immunol
Ano de publicação:
2023
Tipo de documento:
Article