Abstract
T cell Ig and mucin domain (Tim) protein family members were identified to be important regulators of the immune response. As their name indicates, Tim proteins were originally considered a T cell-specific markers, and they mainly regulate the responses of T helper cells. However, accumulating evidence indicates that Tims are also expressed on antigen-presenting cells (APCs), such as monocytes, macrophages, dendritic cells (DCs) and B cells, and even plays various roles in natural killer cells (NKs) and mast cells. In recent years, the expression and function of Tims on different cells and the identification of new ligands for the Tim family have suggested that the Tim family plays a crucial role in immune regulation. In addition, the relationship between Tim family gene polymorphisms and susceptibility to several autoimmune diseases has expanded our knowledge of the role of Tim proteins in immune regulation. In this review, we discuss how the Tim family affects immunomodulatory function and the potential role of the Tim family in typical autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D). A deeper understanding of the immunoregulatory mechanism of the Tim family might provide new insights into the clinical diagnosis and treatment of autoimmune diseases.
Highlights
Autoimmune diseases are characterized by abnormal tolerance to self-antigens that cause damage to body tissues [1]
Considerable progress has been achieved in understanding the expression and function of the T cell Ig and mucin domain (Tim) family in autoimmune diseases
Tim proteins are intimately involved in immunoregulation and participate in many diseases, such as allergies, infections, and cancers, by influencing the immune system
Summary
Autoimmune diseases are characterized by abnormal tolerance to self-antigens that cause damage to body tissues [1]. We focus on the expression and function of Tims on different immune cells, discuss recent studies examining the role of Tims in autoimmune diseases in both animal models and humans, and provide useful insights into the identification of new therapeutic targets. The decreased expression of Tim-3 and CD80 on mast cells and macrophages reduces the level of cytotoxic T lymphocyteassociated protein 4 (CTLA-4) on the surface of CD4+ T cells, resulting in a decrease in the number of Treg cells and aggravated myocarditis [38] These studies indicate that the Tim-3 signaling pathway affects the adaptive immune system by influencing the innate immune system. When Tim-3 does not bind to its ligand, Tyr256/ Tyr263 in the cytoplasmic region of Tim-3 interacts with HLA-B associated transcript 3 (Bat3), and Bat recruits the tyrosine kinases Lck to maintains T cell activation [66]. The findings from these studies enable us to understand the effect of TABLE 2 | Studies examining the roles of Tim family members in autoimmune diseases
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