Resistin-like molecule (RELM)-β is a cysteine-rich cytokine implicated in insulin resistance and asthmatic responses, but its function remains an enigma. We now report that RELM-β has a role in promoting airway inflammation and lung remodeling in the mouse lung. RELM-β is strongly induced by diverse allergens and T helper type 2 (Th2) cytokines by an IL-13- and STAT6-dependent mechanism. To understand the in vivo role of RELM-β, we delivered recombinant murine RELM-β intratracheally to naïve mice. RELM-β induced dose-dependent leukocyte accumulation (most prominently involving macrophages) and goblet cell hyperplasia. The most prominent effect induced by RELM-β was increased perivascular and peribronchial collagen deposition. Mice genetically deficient in RELM-β had reduced accumulation of collagen and goblet cell hyperplasia in an experimental model of allergic airway inflammation. In vitro experiments demonstrated that RELM-β had fibroblast motogenic activity. These results identify RELM-β as a Th2-associated cytokine with potent inflammatory and remodeling activity.
The development of an in vitro 3D model of goblet cell hyperplasia using MUC5AC expression and repeated whole aerosol exposures