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IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells.


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.

SUBMITTER: Brodeur TY 

PROVIDER: S-EPMC4655158 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells.

Brodeur Tia Y TY   Robidoux Tara E TE   Weinstein Jason S JS   Craft Joseph J   Swain Susan L SL   Marshak-Rothstein Ann A  

Journal of immunology (Baltimore, Md. : 1950) 20151030 11


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 inflammatio  ...[more]

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