| First Author | Phong BL | Year | 2015 |
| Journal | J Exp Med | Volume | 212 |
| Issue | 13 | Pages | 2289-304 |
| PubMed ID | 26598760 | Mgi Jnum | J:228938 |
| Mgi Id | MGI:5749877 | Doi | 10.1084/jem.20150388 |
| Citation | Phong BL, et al. (2015) Tim-3 enhances FcepsilonRI-proximal signaling to modulate mast cell activation. J Exp Med 212(13):2289-304 |
| abstractText | T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (FcepsilonRI), using signaling pathways analogous to those in T cells. Using a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcepsilonRI ligation. |
