IL-7 inhibits fibroblast TGF-beta production and signaling in pulmonary fibrosis

The Journal of Clinical Investigation
Min HuangSteven M Dubinett

Abstract

Based on studies by our group and others, we hypothesized that IL-7 may possess antifibrotic activities in an IFN-gamma-dependent and independent manner. Here, we have evaluated the antifibrotic therapeutic potential of IL-7 in both in vitro and in vivo pulmonary fibrosis models. IL-7 inhibited both TGF-beta production and signaling in fibroblasts and required an intact JAK1/STAT1 signal transduction pathway. IL-7-mediated inhibition of TGF-beta signaling was found to be associated with an increase in Smad7, a major inhibitory regulator in the SMAD family. In the presence of IL-7, Smad7 dominant negative fibroblasts restored TGF-beta-induced collagen synthesis, indicating that an IL-7-mediated increase in Smad7 suppressed TGF-beta signaling. Consistent with these in vitro findings, recombinant IL-7 decreased bleomycin-induced pulmonary fibrosis in vivo, independent of IFN-gamma. The antifibrotic activities of IL-7 merit further basic and clinical investigation for the treatment of pulmonary fibrosis.

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Citations

Apr 11, 2009·Archives of Dermatological Research·Oliver Seifert, Ulrich Mrowietz
Nov 13, 2008·Cell Research·Xing Guo, Xiao-Fan Wang
Dec 27, 2011·American Journal of Respiratory and Critical Care Medicine·Yoshinori AonoJo Rae Wright
May 4, 2006·The Journal of Clinical Investigation·M Neale Weitzmann, Roberto Pacifici
Mar 14, 2007·Arthritis Research & Therapy·Roberto Pacifici
Jan 7, 2014·PloS One·Katy M RoachPeter Bradding
May 24, 2014·PLoS Computational Biology·Rodolphe ThiébautYves Lévy
May 16, 2019·Scientific Reports·Stuart M RobinsonJonas Rosendahl
May 8, 2018·The Journal of Clinical Investigation·Loka R PenkeMarc Peters-Golden

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Methods Mentioned

BETA
transfection
ELISA
flow cytometry

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