Interleukin-9 promotes mast cell progenitor proliferation and CCR2-dependent mast cell migration in allergic airway inflammation.

Allergic asthma is a chronic lung disease characterized by airway hyperresponsiveness and cellular infiltration that is exacerbated by IgE-dependent mast cell activation. Interleukin-9 (IL-9) promotes mast cell expansion during allergic inflammation but precisely how IL-9 expands tissue mast cells and promotes mast cell function is unclear. In this report, using multiple models of allergic airway inflammation, we show that both mature mast cells (mMCs) and mast cell precursors (MCp) express IL-9R and respond to IL-9 during allergic inflammation. IL-9 acts on MCp in the bone marrow and lungs to enhance proliferative capacity. Furthermore, IL-9 in the lung stimulates mobilization of CCR2+ mMC from the bone marrow and recruitment to the allergic lung. Mixed bone marrow chimeras demonstrate that these are intrinsic effects in the MCp and mMC populations. IL-9-producing T cells are both necessary and sufficient to increase mast cell numbers in the lung in the context of allergic inflammation. Importantly, T cell IL-9-mediated mast cell expansion is required for the development of antigen-induced and mast cell-dependent airway hyperreactivity. Collectively, these data demonstrate that T cell IL-9 induces lung mast cell expansion and migration by direct effects on the proliferation of MCp and the migration of mMC to mediate airway hyperreactivity.