Tim-3: An Activation Marker and Activation Limiter of Innate Immune Cells

Abstract

Tim-3 was initially identified on activated Th1, Th17, and Tc1 cells and induces T cell death or exhaustion after binding to its ligand, Gal-9. The observed relationship between dysregulated Tim-3 expression on T cells and the progression of many clinical diseases has identified this molecule as an important target for intervention in adaptive immunity. Recent data have shown that it also plays critical roles in regulating the activities of macrophages, monocytes, dendritic cells, mast cells, natural killer cells, and endothelial cells. Although the underlying mechanisms remain unclear, dysregulation of Tim-3 expression on these innate immune cells leads to an excessive or inhibited inflammatory response and subsequent autoimmune damage or viral or tumor evasion. In this review, we focus on the expression and function of Tim-3 on innate immune cells and discuss (1) how Tim-3 is expressed and regulated on different innate immune cells; (2) how it affects the activity of different innate immune cells; and (3) how dysregulated Tim-3 expression on innate immune cells affects adaptive immunity and disease progression. Tim-3 is involved in the optimal activation of innate immune cells through its varied expression. A better understanding of the physiopathological role of the Tim-3 pathway in innate immunity will shed new light on the pathogenesis of clinical diseases, such as autoimmune diseases, chronic viral infections, and cancer, and suggest new approaches to intervention.

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

“…Tim-3, one of the most important members of this family, is primarily expressed in CD8 + T cells, monocytes, dendritic cells, and mast cells. Tim-3 is a specific surface marker of Th1 cells, and regulates autoimmune and allergic disease by mediating the immune response of Th1 cells (Han et al, 2013;Anderson, 2014). Furthermore, Tim-3 was found to be closely related to the occurrence and development of several types of cancer, including prostate cancer, non-small cell cancer, cervical cancer, and melanoma (Geng et al, 2006;Cao et al, 2013).…”

The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal–fetal interface in early pregnancy

“…Increasing numbers of studies have shown that abnormal expression of Tim-3 is an important cause of autoimmune diseases, infections, transplantation problems and cancers. 24 Recent data have shown that NK cells can also be regulated by Tim-3. Tim-3 was found to act as a marker of activation or maturation of NK cells and suppress NK cell cytotoxicity.…”

Blocking monoclonal antibodies of TIM proteins as orchestrators of anti-tumor immune response

“…40 TIM-3 plays important roles in the regulation of both arms of innate and adaptive immunity. 41,42 In tumors, TIM-3 expression is induced in innate immune cells, e.g., dendritic cells and macrophages, by tumor-released factors such as interleukin (IL)-10 and vascular endothelial growth factor, leading to a suppression of innate responses to nucleic acids released from apoptotic tumor cells by interacting with HMGB1. 44 Additionally, TIM-3 serves as an exhaustion marker for T cells in tumors.…”