The Role of T cell Immunoglobulin and Mucin Domain‐3 in Immune Thrombocytopenia

Abstract

T cell immunoglobulin and mucin domain-3 (TIM-3), originally identified as a T helper (Th) 1-specific type I membrane protein, plays a vital role in Th1 immunity and tolerance induction through interaction with its ligand, galectin-9. The binding of TIM-3 by galectin-9 serves to downregulate Th1 responses. Moreover, the regulatory function of TIM-3 has been extended to other cells, such as Th17 cells, CD4 + CD25 + regulatory T cells (Tregs), CD8 + T cells and certain innate immune cells. Previous studies have acknowledged that the TIM-3 pathway is involved in the pathogenesis of several human autoimmune diseases, such as systemic lupus erythematous, rheumatoid arthritis and aplastic anaemia. Moreover, genetic data suggest a role for TIM-3 in human autoimmune diseases. However, in immune thrombocytopenia (ITP), a common Th1-and possibly Th17-biased autoimmune disorder, the role of TIM-3 has not been explored. Recently, our data have demonstrated that TIM-3 expression is reduced in ITP patients, and we have found a potential link between ITP and the TIM-3 pathway. In this article, we discuss and speculate on the role of the TIM-3 pathway in ITP.

Decreased Expression of TIM-3 on Th17 Cells Associated with Ophthalmopathy in Patients with Graves’ Disease.

“…Reduced expression of TIM-3 and galectin-9 in TAO patients represented a weakened negative regulation mechanism. As has been observed in other autoimmune diseases [ 16 , 30 ], it could result in the failure of peripheral tolerance, and enhanced inflammatory activities of Th1 and Th17 cells. It was also in accordance with previous findings regarding increased levels of Th1 and Th17 cytokines [ 8 ].…”

Effects of Tim-3 silencing on the viability of fibroblast-like synoviocytes and lipopolysaccharide-induced inflammatory reactions

“…Tim-3 is also expressed on the surface of innate immune cells, including CD 4+ T cells, CD 8+ T cells, monocytes, B cells and natural killer cells (19). Typically, abnormalities of Tim-3 signaling pathway are associated with allergic, autoimmune and viral infectious diseases, including asthma, systemic lupus erythematosus, RA and aplastic anemia (16,17). Tim-3 potentially modulates the immune response by negatively regulating Th1 to inhibit the inflammatory reaction.…”

“…This gene family is located on human chromosome 5 and 3 different subtypes have been identified so far: Tim-1, Tim-2 and Tim-3 (15). Tim-3 is considered to be a specific surface marker of Th1 cells and is able to regulate the immune response of Th1 cells to participate in systemic lupus erythematosus, aplastic anemia and other autoimmune diseases (16,17). Furthermore, Tim-3 is highly expressed in cluster of differentiation (CD)4 + T cells, as well as the synovial tissue of patients with RA (17)(18)(19).…”

Effects of T cell immunoglobulin and mucin domain-containing molecule-3 signaling molecule on human monocyte-derived dendritic cells with hepatitis B virus surface antigen stimulation in vitro

“…T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3), a member of the Tim family, was found to be involved in the pathogenesis of numerous diseases, including virus infections, cancer, autoimmune diseases, and also allergic reactions and transplantation rejection (13). Khademi et al (14) first reported the high mRNA expression levels of Tim-3 in human T helper 1 cells (Th1) in vitro, therefore Tim-3 was initially considered as a special membrane protein expressed on the Th1 cells (15); however, it was revealed that Tim-3 was also expressed on other cell types, including cluster of differentiation (CD)8+T, Th17, nature killer (NK), mast, endothelial and regulatory cells, as well as monocytes, macrophages, DCs and neurogliocytes (13). A previous study showed that Tim-3 was also expressed in tumor cells and could serve as an independent prognostic factor for cancer (16).…”