IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells.
J Immunol
; 195(11): 5251-60, 2015 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-26519529
ABSTRACT
Type 2 effector production of IL-13, a demonstrated requirement in models of fibrosis, is routinely ascribed to CD4(+) Th2 cells. We now demonstrate a major role for CD8(+) T cells in a murine model of sterile lung injury. These pulmonary CD8(+) T cells differentiate into IL-13-producing Tc2 cells and play a major role in a bleomycin-induced model of fibrosis. Differentiation of these Tc2 cells in the lung requires IL-21, and bleomycin treated IL-21- and IL-21R-deficient mice develop inflammation but not fibrosis. Moreover, IL-21R-expressing CD8(+) cells are sufficient to reconstitute the fibrotic response in IL-21R-deficient mice. We further show that the combination of IL-4 and IL-21 skews naive CD8(+) T cells to produce IL-21, which, in turn, acts in an autocrine manner to support robust IL-13 production. Our data reveal a novel pathway involved in the onset and regulation of pulmonary fibrosis and identify Tc2 cells as key mediators of fibrogenesis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibrosis Pulmonar
/
Linfocitos T Citotóxicos
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Interleucinas
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Interleucina-13
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Subunidad alfa del Receptor de Interleucina-21
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2015
Tipo del documento:
Article