Disease relevance of HAVCR2

• TIM-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with TIM-3 ligand to regulate Th1 responses [1].
• Most importantly, recent data suggest a novel paradigm in which dysregulation of the TIM-3-galectin-9 pathway could underlie chronic autoimmune disease states, such as multiple sclerosis [2].
• 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) [3].
• The 3 tested single nucleotide polymorphisms (SNPs) in TIM 3 were significantly related to atopy and eczema [4].
• We investigated the ability of Abs blocking Tim-1 or Tim-3 ligand-binding activity to prevent and treat murine experimental allergic conjunctivitis (EC), a Th2-mediated disease [5].
• These data provide functional, mechanistic data for dysregulated TIM-3 immunoregulation in a human autoimmune disease and suggest that approved therapies for the treatment of MS may function in part by restoring TIM-3 immunoregulation of T cell function [6].

High impact information on HAVCR2

• 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].
• Dysregulated T cell expression of TIM3 in multiple sclerosis [8].
• TIM-3 is similarly expressed on human Th1 cells and not on Th2 cells, which suggests that TIM-3 might also contribute to Th1 regulation in humans [2].
• Tim-3 ligand expression was also up-regulated in splenic T cells, DCs, and macrophages, but not in the hepatic lymphocytes [3].
• None of the 3 variants in TIM-3 genes yielded significant association with either asthma or asthma-related phenotypes [9].

Chemical compound and disease context of HAVCR2

• We evaluated the pharmacokinetic properties of Kryobulin TIM3, a new heat-treated Factor VIII concentrate which has recently become available in Europe. Twelve patients with classic hemophilia were studied [10].

Biological context of HAVCR2

• In the present study, we analyzed the association of the genotype and allele frequencies between asthma or allergic rhinitis patients and nonatopic controls using large samples size at -1516G > T, -574T > G, and 4259G > T polymorphic sites of the Tim-3 gene [11].
• TIM-3 in autoimmunity [2].
• 3. Stimulation of Tim-3 by its ligand galectin-9 results in increased phosphorylation of Y265, suggesting that this tyrosine residue plays an important role in downstream signalling events regulating T-cell fate [12].
• Binding of galectin-9 to the extracellular domain of Tim-3 results in apoptosis of T(H)1 cells, but the intracellular pathways involved in the regulatory function of Tim-3 are unknown [12].
• 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 [3].

Anatomical context of HAVCR2

• A member of TIM family, TIM-3 is selectively expressed on the surface of differentiated Th1 cells [1].
• Unlike Tim-1, which is expressed in renal epithelia and cancer, Tim-3 has not been described in cells other than neuronal or T-cells [12].
• We have cloned Tim-3 from an immortalized liver cell carcinoma line and identified a highly conserved tyrosine in the intracellular tail of Tim-3 (Y265) [12].
• In the current review, we provide evidences indicating that TIM-3 is capable of modulating the function of CD4(+)CD25(+) regulatory T cells and inhibiting aggressive Th1 mediated auto- and allo-immune responses [13].
• Human Tim-3 mRNA was highly expressed in monocytes or monocyte-derived cells, and the expression level decreased when DC underwent maturation and activation [14].

Associations of HAVCR2 with chemical compounds

• A highly conserved tyrosine of Tim-3 is phosphorylated upon stimulation by its ligand galectin-9 [12].
• Human Tim-3 is a 301-residue type I membrane protein whose extracellular region contains a Cys-rich Ig-like domain and a mucin domain, the characteristics of Tim proteins [14].

Other interactions of HAVCR2

• These results strongly suggest that -574T>G and 4259G>T polymorphism of the Tim-3 might be associated with susceptibility to RA [1].
• Our results strongly suggest that the -574T > G polymorphism of Tim-3 might be associated with the susceptibility of atopic diseases such as asthma and allergic rhinitis [11].
• In tuberculous pleural effusion, ratios of IFN-gamma and IL-12 to IL-4 were significantly higher, and T-cells showed the expression of Tim-3 messenger RNA [15].
• These positive costimulatory signals are counterbalanced by signals that dampen down immune responses and include CTLA-4, PD-1 and the recently described Ig superfamily members BTLA and TIM-3 [16].

Analytical, diagnostic and therapeutic context of HAVCR2

• Using RT-PCR we demonstrate that Tim-3 is expressed in malignant and non-malignant epithelial tissues [12].
• We demonstrated that HeLa cells, which are refractory to HAV infection, acquired a limited susceptibility to HAV infection after stably overexpressing human Tim-3 as confirmed by Western blot analysis using anti-Tim-3 antibody, but Tim-3-Fc fusion protein had no direct HAV-binding activity [14].

References