The Modulation of Pulmonary Fibrosis by IL - 13 Rα 2

24 Pulmonary Fibrosis is a progressive and fatal disease that involves the remodelling of the 25 distal airspace and the lung parenchyma which results in compromised gas exchange. The 26 median survival time once diagnosed is less than 3 yrs. IL-13 has been shown to play a role 27 in a number of inflammatory and fibrotic diseases. IL-13 modulates its effector functions via 28 a complex receptor system that includes the IL-4Rα, IL-13Rα1 and the IL-13Rα2. IL-13Rα1 29 binds IL-13 with low affinity yet when it forms a complex with IL-4α, it binds with much 30 higher affinity inducing the effector functions of IL-13. IL-13Rα2 binds IL-13 with high 31 affinity but has a short cytoplasmic tail and has been shown to act as a non-signalling decoy 32 receptor. Transfection of fibroblasts and epithelial cells with IL-13Rα2 inhibited the IL-13 33 induction of soluble collagen, TGF-β and CCL17. Adenoviral overexpression of IL-13Rα2 in 34 the lung reduced bleomycin induced fibrosis. Our work shows that overexpression of IL35 13Rα2 inhibits the IL-13 induction of fibrotic markers in vitro and inhibits bleomycin 36 induced pulmonary fibrosis. In summary our study highlights the antifibrotic nature of IL37 13Ra2. 38