A role for Hox5 genes in T cell function during chronic allergic inflammation (HYP7P.268)

Abstract

Abstract Allergic asthma is a significant health burden in western countries, and continues to increase in prevalence. T helper 2 (Th2) cells contribute to the development of disease through release of the cytokines interleukin (IL)-4, IL-5 and IL-13, resulting in increased airway eosinophils and mucus hypersecretion. While many factors are involved in the development of allergic asthma, the molecular mechanisms behind the disease remain largely unknown. As the three members of the Hox5 gene family (Hoxa5, Hoxb5 and Hoxc5) have been shown to play a role in lung development, we asked whether these genes also play a role in the adult lung in response to disease. We found that Hox5-deficient mice show exacerbated pathology compared to wild-type controls in a chronic allergen model, with an increased Th2 response as well as changes in lung tissue pathology. Examination of T cells from naïve wild-type or Hox5-deficient mice in Th2 polarizing conditions showed increased proliferation, enhanced Gata3 expression and production of IL-4, IL-5 and IL-13 in Hox5-deficient mice compared to wild-type controls. Overexpression of FLAG-tagged HOX5 proteins in Jurkat cells demonstrated HOX5 binding to the Gata3 locus, supporting a role for HOX5 proteins in direct transcriptional control of Th2 development. These results reveal a novel role for Hox5 genes as developmental regulators of immune cell function and Th2-induced pathology during allergic disease in the lung.