Regulation of TIM-3 Expression in Mast cells and Monocytes

Abstract

T cell immunoglobulin mucin domain 3 (TIM-3) which is a type-I membrane protein, is expressed on differentiated Th1 cell, mast cell and monocyte. Although expression of TIM-3 and its ligand galectin-9 has been demonstrated in mast cells, the transcriptional regulation of these molecules has not been well explored. Considering the emerging role of mast cells in host defense, I studied the effect of various cytokines, a TLR agonist or FcεR stimulation on transcription levels of TIM-3 and galectin-9 in a human mast cell line, HMC-1 cells. TIM-3 transcription in HMC-1 cell was upregulated only by TGF-b but not by IFN-a, IFN-l, TNF-a, IL-10, LPS or FcεR cross-linking. Whereas transcription of TIM-3 ligand, galectin-9 was not affected by treatment with TGF-b. To reveal downstream pathway of TGF-b stimulation involved in TIM-3 upregulation in HMC-1 cells, I examined MAPK pathway and the role of GATA-1. I demonstrated that TGF-b mediated TIM-3 upregulation was inhibited both by a inhibitor of ERK but not by inhibitors of p38 and JNK. Further, overexpression of GATA-1 did not affect TIM-3 expression in HMC-1 cells. These results suggest that TIM-3 transcription in mast cells may be upregulated by TGF-b through ERK MAP kinase signal.