TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells Short title: Role of TIM-1 and TIM-3 in mast cell function

Members of the T cell immunoglobulinand mucin-domain-containing molecule (TIM) family have roles in T cell-mediated immune responses. TIM-1 and TIM-2 are predominantly expressed on Th2 cells, whereas TIM-3 is preferentially expressed on Th1 and Th17 cells. We found that TIM-1 and TIM-3, but neither TIM-2 nor TIM-4, were constitutively expressed on mouse peritoneal mast cells and bone-marrow-derived cultured mast cells (BMCMCs). After IgE+Ag stimulation, TIM-1 expression was downregulated on BMCMCs, whereas TIM-3 expression was upregulated. We also found that recombinant mouse TIM-4 (rmTIM-4), which is a ligand for TIM-1, as well as an anti-TIM-3 polyclonal Ab, can promote IL-4, IL-6 and IL-13 production without enhancing degranulation in BMCMCs stimulated with IgE+Ag. Moreover, the anti-TIM-3 Ab, but neither anti-TIM-1 Ab nor rmTIM-4, suppressed mast cell apoptosis. These observations suggest that TIM-1 and TIM-3 may be able to influence T cell-mediated immune responses in part through effects on mast cells. For personal use only. on October 28, 2017. by guest www.bloodjournal.org From