IL-13 signaling through the IL-13α2 receptor is involved in induction of TGF-β1 production and fibro

Abstract

Interleukin (IL)-13 is a major inducer of fibrosis in many chronic infectious and autoimmune diseases. In studies of the mechanisms underlying such induction, we found that IL-13 induces transforming growth factor (TGF)-β1 in macrophages through a two-stage process involving, first, the induction of a receptor formerly considered to function only as a decoy receptor, IL-13Rα2. Such induction requires IL-13 (or IL-4) and tumor necrosis factor (TNF)-α. Second, it involves IL-13 signaling through IL-13Rα2 to activate an AP-1 variant containing c-jun and Fra-2, which then activates the TGFB1 promoter. In vivo, we found that prevention of IL-13Rα2 expression reduced production of TGF-β1 in oxazolone-induced colitis and that prevention of IL-13Rα2 expression, Il13ra2 gene silencing or blockade of IL-13Rα2 signaling led to marked downregulation of TGF-β1 production and collagen deposition in bleomycin-induced lung fibrosis. These data suggest that IL-13Rα2 signaling during prolonged inflammation is an important therapeutic target for the prevention of TGF-β1–mediated fibrosis.

Cite this article

Fichtner-Feigl, S., Strober, W., Kawakami, K. et al. IL-13 signaling through the IL-13α₂ receptor is involved in induction of TGF-β₁ production and fibrosis. Nat Med 12, 99–106 (2006). https://doi.org/10.1038/nm1332

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