Generation of mice with a conditional Il9 allele

Abstract

Abstract Interleukin (IL)-9 is a pleotropic cytokine that induces cell-specific functions associated with asthma, with target cells including T cells, mast cells, eosinophils, and epithelial cells. Previous findings have demonstrated that IL-9 promotes mast cell growth and differentiation, suggesting that IL-9 contributes to mast cell-driven allergic diseases. Although studies have demonstrated the impact of IL-9 in allergic asthma and other allergic diseases, the cellular source of IL-9 in each setting remains unclear. IL-9 can be produced by several cell types including natural killer T cells, innate lymphoid cells, mast cells, and CD4+ T helper cells (Th). We speculate that T helper 9 (Th9) cells are a major source of IL-9 and that Th9-dervied IL-9 promotes mast cell expansion, activity, and function. Our hypothesis is supported by findings in patients with asthma in which IL-9 expression and Th9 cell numbers are significantly elevated. Here, we address the role of T cell–derived IL-9 in mice with an inactivation of the IL-9 gene restricted to T cells generated by CD4-Cre/loxP-mediated targeting of the IL-9 gene. Preliminary results demonstrate efficient deletion of Il9 in T cells. Il9 fl/fl CD4-Cre Th9 cultures have minimal production of IL-9. Ongoing studies will directly examine the contribution and function of TH9-derived IL-9 during models of allergic airway inflammation and future studies will define the requirement for IL-9 in other cell populations during allergic immune responses.