Disease relevance of Havcr2

• Tim-3 may have an important role in the induction of autoimmune diseases by regulating macrophage activation and/or function [1].
• Dysregulated T cell expression of TIM3 in multiple sclerosis [2].
• TIM-3 has been shown to be expressed on murine Th1 cell clones and has been implicated in the pathogenesis of Th1-driven experimental autoimmune encephalomyelitis [3].
• We examined Tim-3 and its ligand expression as well as the effects of anti-Tim-3 mAb treatment in a murine model of acute graft-vs-host disease (aGVHD) [4].
• We show in this study that reducing Tim-3 signaling during the innate immune response to viral infection in BALB/c mice reduces CD80 costimulatory molecule expression on mast cells and macrophages and reduces innate CTLA-4 levels in CD4+ T cells, resulting in decreased T regulatory cell populations and increased inflammatory heart disease [5].
• Blocking Tim-3 function has a beneficial effect during pulmonary inflammation by skewing the Th2 response toward that of a Th1 type, suggesting an important role for Tim-3 in the regulation of allergic disease [6].

High impact information on Havcr2

• Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease [1].
• In vivo administration of antibody to Tim-3 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease, and increases the number and activation level of macrophages [1].
• Genomic association of the TIM family and polymorphisms in both Tim-1 and Tim-3 in different immune-mediated diseases suggest that the family may have an important role in regulating immunity, both in terms of normal immune responses and in diseases like autoimmunity and asthma [7].
• Fusion proteins (Tim-3-Ig) of both Tim-3 isoforms specifically bound CD4(+) T cells, indicating that a Tim-3 ligand is expressed on CD4(+) T cells [8].
• These results indicate that regulation of inflammation in the heart begins during innate immunity and that Tim-3 signaling on cells of the innate immune system critically influences regulation of the adaptive immune response [5].

Biological context of Havcr2

• T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified [8].
• Our results suggest that Tim-3 may play a crucial role in the regulation of CD8(+) T cells responsible for the maintenance of hepatic homeostasis and tolerance [4].
• The chromosome 11 QTL co-localizes with eae6b, and with Il12b and heptatitis A virus cellular receptor 2 (Havcr2, formerly known as Timd3), both of which are candidate genes for this QTL [9].
• In this study, a cellular surface membrane protein of immunoglobulin (Ig) superfamily (IgSF) was identified from a human dendritic cell (DC) cDNA library by large-scale random sequencing, which is identical to previously reported Tim-3 (T-cell Ig- and mucin-domain-containing molecule 3) [10].
• CONCLUSIONS: A transient upregulation of Tim-3 expression was observed in the early stage of ACAID, suggesting its possible involvement in the development of ACAID [11].

Anatomical context of Havcr2

• We report here that the T(H) type 1 (T(H)1)-specific Tim-3 (T cell immunoglobulin domain, mucin domain) protein functions to inhibit aggressive T(H)1-mediated auto- and alloimmune responses [12].
• Tim-3 ligand expression was also up-regulated in splenic T cells, DCs, and macrophages, but not in the hepatic lymphocytes [4].
• T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3) and TIM-1 molecules are differentially expressed on human Th1 and Th2 cells and in cerebrospinal fluid-derived mononuclear cells in multiple sclerosis [3].
• PURPOSE: To assess the expression of T-cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) in the spleens of BALB/c mice undergoing anterior chamber-associated immune deviation (ACAID) [11].
• Whereas lesional macrophage content, aortic CD4, and Th1-related Tim3 expression were reduced, smooth muscle cell (SMC) content and expression of interleukin-10 in plaques, lesional SMCs, and splenocytes were elevated [13].

Other interactions of Havcr2

• Using real-time (TaqMan) RT-PCR, we show that human Th1 lines expressed higher TIM-3 mRNA levels, while Th2 lines demonstrated a higher expression of TIM-1 [3].

Analytical, diagnostic and therapeutic context of Havcr2

• Tim-3 pathway blockade accelerated diabetes in nonobese diabetic mice and prevented acquisition of transplantation tolerance induced by costimulation blockade [12].

References