Human mast cells and type 2 innate lymphoid cells activate gene expression and mucus composition in human bronchial epithelial cells via IL-13

Background: Mechanisms driving asthma exacerbationsare not well understood. Epithelial cells are primary responders to invading pathogens. Type 2 cytokine producing cells including mast cellsare found in airway epithelium of asthmatics; innate type 2 lymphoid cells (ILC2s) contribute to type 2 inflammation in mouse asthma models and have been found in adult human lungs. Objectives: Understanding mechanisms by which effector cells including mast cellsand ILC2s may act on bronchial epithelium to exacerbate airway pathology. Methods: Normal human bronchial epithelial cells (NHBE) were cultured at air-liquid interface. Peripheral blood CD34+ cell derived human mast cellsor lineage - CRTH2 + CD161 + CD127 + ILC2s were added basolaterally, and stimulated with either IL-33 or control media, alone or in combination with anti-IL-13 for 72 hours. Effects on NHBE were assessed via gene expression. Results: IL-33 significantly enhanced IL-13 production in mast cells. Expression of CCL26, MUC5AC, and periostinwas significantly upregulated in IL-13 treated NHBE and in NHBE co-cultured with IL-33 stimulated mast cells, compared to control. NHBE responses were significantly attenuated with addition of anti-IL-13 to the IL-33 treated mast cells. Co-culture of ILC2s with NHBE strongly upregulated CCL26, MUC5AC, and periostinexpression in NHBE, and responses were suppressed by the addition of anti-IL-13. Similar patterns were observed via microarray analysis. Conclusions: IL-13 from activated mast cellsand ILC2s may amplify airway inflammation in asthmatics by increasing cytokine expression and mucus secretion, contributing to increased airway obstruction.