Induction of CXCL3 in airway epithelial cells by a novel IL-9 receptor complex 

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Presentation Time: 04:45 PM - 05:00 PM
Abstract ID: 4738 - B

Presenting Author:
Cherry Cheuk Lam Cheung , PhD Candidate at Indiana Univ. Sch. of Med.

Abstract:

Cytokine signaling is critical for cell-to-cell communication in development, homeostasis and disease. Interleukin (IL)-9 signaling promotes allergic diseases by acting on both immune and structural cells. In hematopoietic cells, IL-9 receptor (IL-9R) consists of two subunits – the α-chain (IL-9Rα) and a common γ (γc) chain. However, IL-9-responsive epithelial cells express IL-9Rα but not the γc chain raising a question on how these cells respond to IL-9 in the absence of the established IL-9R complex. Here, we discovered that in airway epithelial cells, IL-9Rα pairs with IL-13Rα1, forming a novel type II IL-9R. Using proximity ligation assay, we show that the IL-9Rα /IL-13Rα1 chains are in IL-9-dependent proximity in both mouse tracheal epithelial cells (mTEC) and human small airway epithelial cells (SAEC). IL-9-induced STAT3 activation in SAEC was blocked by anti-IL-13Rα1 but not by anti-γc. Using RNA-seq, in vitro IL-9 treatment of SAEC induced the expression of genes including CXCL3, a key chemokine implicated in asthma. Importantly, intranasal administration of IL-9 increased Cxcl3 expression in mTECs and CXCL3 protein in the lung, that corresponds with an expansion in the number of CXCR2+ immune cells in the lung. Thus, we identify a novel type II IL-9R which is composed of IL-9Rα and IL-13Rα1 and show that IL-9 signaling via type II IL-9R induces CXCL3 expression in epithelial cells to contribute to airway inflammation.