The role of Th2 cytokines in mast cell homeostasis

Homeostatic mechanisms regulating mast cell numbers and function in periphe ral tissues have largely focused on cytokines, such as stem cell factor, in terleukin (IL)-3, IL-4, and IL-10, which regulate mast cell maintenance and proliferation. Despite these advances, little attention has been paid to t he mechanisms that mediate mature mast cell turnover, and control of mast c ell hyperplasia generated during Th2-mediated responses. These are importan t issues, as mast cells are now known to be multi-functional effector cells , that have the capacity to mediate both innate and Th2-induced immune resp onses. Numerous secretagogues may elicit mast cells to release a large numb er of important mediators that can cause chronic inflammation. Therefore, h ow mast cell homeostasis is regulated may have significant effects on norma l physiology, and contribute to the genesis of inflammatory disease. Our la boratory has characterized an in vitro model of mast cell homeostasis, by w hich long-term exposure of murine bone-marrow-derived mast cells to the Th2 -derived cytokines IL-3, IL-4, and IL-10, will induce downregulation of cri tical mast cell effector proteins such as Kit and Fc epsilon RI, followed b y mast cell apoptosis. These data offer a novel role for Th2 cytokines, act ing to both initiate and resolve mast cell activation and proliferation. Lo ss of these signals may contribute to a multitude of diseases, such as mast ocytosis and allergy.