The role of IL-9 secreting CD4+ T helper cells in promoting mast cell expansion in pulmonary models of inflammation

Abstract

Abstract Mast cells are tissue resident cells with granules that contain histamine and other proinflammatory mediators. Mast cells are important effectors in immediate type I hypersensitivity reactions. In severe allergic reactions, immunoglobulin E (IgE)-mediated mast cell degranulation triggers localized and systemic anaphylaxis. In allergic asthma, mast cells and T cells interact in the generation of long-lasting inflammation. The molecular mechanisms responsible for mast cell expansion has not been fully elucidated. Because T cells are an important source of the mast cell growth factor IL-9, we are interested in understanding the role of IL-9, and IL-9-producing T cells in mast cell expansion and recruitment. We have identified a role of T helper 9 (Th9) cells in influencing mast cell number and function in pulmonary models of inflammation. Using adoptive transfer models, we have defined a contribution of Th9 cells in immediate hypersensitivity. We have demonstrated that IL-9 expands mast cell progenitor numbers in bone marrow and lung, suggesting that there are systemic effects of local IL-9 production. We hypothesize that increased mature mast cells in the pulmonary system are from recruitment and expansion of progenitor cells rather than expansion of mature cells in situ. Ongoing studies will directly examine the relative contribution and function of the two populations during models of allergic airway inflammation.