Development of strategy to treat allergic diseases via targeting surface molecules on lymphocytes and intracellular signaling molecules

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Members of the T-cell immunoglobulin mucin (Tim) family control a variety of immune responses including Th1 and Th2 differentiation of T cells. We found that TIM-3 was expressed on C8+ dendritic cells (DC) and TIM-3 was crucial for clearance of apoptotic cells by phagocytes. Moreover, TIM-3-dependent phagocytosis of apoptotic cells was crucial for cross-presentation of dying cell-associated antigens. On the other hand, TIM-2 was found to be expressed on B cells and induced positive signals into B cells. Therefore, administration of agonistic anti-TIM-2 antibody significantly exacerbated type II collagen-induced arthritis. We next investigated a role for autophagy in the development and function of mast cells. We found that conversion of type I to type II light chain (LC3)-II, a hallmark of autophagy, was constitutively induced in mast cells under full nutrient conditions, and LC3-II localized in secretory granules of mast cells. Although deletion of Atg7 did not impair the development of BMMCs, Atg7(-/-) BMMCs showed severe impairment of degranulation, but not cytokine production upon antigen stimulation.