Genomes and Genes
Gene Symbol: Tim 3
Description: hepatitis A virus cellular receptor 2
Alias: CD366, HAVcr-2, KIM-3, TIM3, TIMD-3, TIMD3, Tim-3, hepatitis A virus cellular receptor 2, T cell immunoglobulin mucin 3, T-cell immunoglobulin and mucin domain-containing protein 3, T-cell immunoglobulin mucin family member 3, T-cell immunoglobulin mucin receptor 3, T-cell membrane protein 3, kidney injury molecule-3
Products: Tim 3
- Cao Y, Zhou X, Huang X, Li Q, Gao L, Jiang L, et al. Tim-3 expression in cervical cancer promotes tumor metastasis. PLoS ONE. 2013;8:e53834 pubmed publisher..Our study suggests that the expression of Tim-3 in tumor cells may be an independent prognostic factor for patients with cervical cancer. Moreover, Tim-3 expression may promote metastatic potential in cervical cancers. ..
- Yang Z, Grote D, Ziesmer S, Niki T, Hirashima M, Novak A, et al. IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma. J Clin Invest. 2012;122:1271-82 pubmed publisher..Our findings identify IL-12- and TIM-3-mediated exhaustion of T cells as a mechanism for poor clinical outcome when IL-12 is administered to FL patients. ..
- Lee J, Su E, Zhu C, Hainline S, Phuah J, Moroco J, et al. Phosphotyrosine-dependent coupling of Tim-3 to T-cell receptor signaling pathways. Mol Cell Biol. 2011;31:3963-74 pubmed publisher..These findings should help further the study of Tim-3 function in other physiological settings, such as those that lead to immune exhaustion. ..
- Zhang Y, Ma C, Wang J, Ji X, Wu X, Moorman J, et al. Tim-3 regulates pro- and anti-inflammatory cytokine expression in human CD14+ monocytes. J Leukoc Biol. 2012;91:189-96 pubmed publisher..These results suggest that Tim-3 has a role as a regulator of pro- and anti-inflammatory innate immune responses. ..
- Anderson A, Anderson D, Bregoli L, Hastings W, Kassam N, Lei C, et al. Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science. 2007;318:1141-3 pubmed..Thus, by virtue of differential expression on innate versus adaptive immune cells, Tim-3 can either promote or terminate TH1 immunity and may be able to influence a range of inflammatory conditions. ..
- Tong D, Zhou Y, Chen W, Deng Y, Li L, Jia Z, et al. T cell immunoglobulin- and mucin-domain-containing molecule 3 gene polymorphisms and susceptibility to pancreatic cancer. Mol Biol Rep. 2012;39:9941-6 pubmed..07, 95 % CI, 1.41-6.68, p = 0.003). These results suggested polymorphisms in TIM-3 gene could be new risk factors for the development of pancreatic cancer. ..
- Wu W, Shi Y, Li J, Chen F, Chen Z, Zheng M. Tim-3 expression on peripheral T cell subsets correlates with disease progression in hepatitis B infection. Virol J. 2011;8:113 pubmed publisher..Our results suggest that over-expression of Tim-3 is involved in disease progression of CHB and that Tim-3 may participate in skewing of Th1/Tc1 response, which contributes to persistency of HBV infection. ..
- Gao X, Zhu Y, Li G, Huang H, Zhang G, Wang F, et al. TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression. PLoS ONE. 2012;7:e30676 pubmed publisher..Our study reveals a new role of TIM-3 as an important immune regulator in the tumor microenvironment via its predominant expression in regulatory T cells. ..
- Khademi M, Illes Z, Gielen A, Marta M, Takazawa N, Baecher Allan C, et al. 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. J Immunol. 2004;172:7169-76 pubmed..These data imply the differential expression of human TIM molecules by Th1 and Th2 cells and may suggest their differential involvement in different phases of a human autoimmune disease. ..
- Naka E, Ponciano V, Cenedeze M, Pacheco Silva A, Camara N. Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode. Int Immunopharmacol. 2009;9:658-62 pubmed publisher..Moreover, there was a positive correlation between galectin-9 and Tim-3 mRNA levels. The simultaneous expression of galectin-9 and Tim-3 may indicate an immunoregulatory function, during the ongoing cytotoxic response. ..
- CHO J, Roche M, Sandall B, Brass A, Seed B, Xavier R, et al. Enhanced Tim3 activity improves survival after influenza infection. J Immunol. 2012;189:2879-89 pubmed publisher..T cell Ig and mucin domain 3 (Tim3) is a negative regulator of Th1/Tc1-type immune responses...
- Golden Mason L, Palmer B, Kassam N, Townshend Bulson L, Livingston S, McMahon B, et al. Negative immune regulator Tim-3 is overexpressed on T cells in hepatitis C virus infection and its blockade rescues dysfunctional CD4+ and CD8+ T cells. J Virol. 2009;83:9122-30 pubmed publisher..These findings have implications for the development of novel immunotherapeutic approaches to this common viral infection. ..
- DeKruyff R, Bu X, Ballesteros A, Santiago C, Chim Y, Lee H, et al. T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells. J Immunol. 2010;184:1918-30 pubmed publisher..These findings establish a new paradigm for TIM proteins as PtdSer receptors and unify the function of the TIM gene family, which has been associated with asthma and autoimmunity and shown to modulate peripheral tolerance. ..
- Huang X, Bai X, Cao Y, Wu J, Huang M, Tang D, et al. Lymphoma endothelium preferentially expresses Tim-3 and facilitates the progression of lymphoma by mediating immune evasion. J Exp Med. 2010;207:505-20 pubmed publisher..These findings highlight a novel molecular mechanism that is a potential target for enhancing the efficacy of tumor immunotherapy and controlling metastatic diseases...
- Dardalhon V, Anderson A, Karman J, Apetoh L, Chandwaskar R, Lee D, et al. Tim-3/galectin-9 pathway: regulation of Th1 immunity through promotion of CD11b+Ly-6G+ myeloid cells. J Immunol. 2010;185:1383-92 pubmed publisher..Our data uncover a novel mechanism by which the Tim-3/Gal-9 pathway regulates immune responses and identifies this pathway as a therapeutic target in diseases where myeloid-derived suppressor cells are disadvantageous. ..
- Sada Ovalle I, Chávez Galán L, Torre Bouscoulet L, Nava Gamiño L, Barrera L, Jayaraman P, et al. The Tim3-galectin 9 pathway induces antibacterial activity in human macrophages infected with Mycobacterium tuberculosis. J Immunol. 2012;189:5896-902 pubmed publisherT cell Ig and mucin domain 3 (Tim3) is an inhibitory molecule involved in immune tolerance, autoimmune responses, and antiviral immune evasion...
- Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka Akita H, et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012;13:832-42 pubmed publisher..Our findings define a mechanism whereby tumor microenvironments suppress antitumor immunity mediated by nucleic acids. ..
- van de Weyer P, Muehlfeit M, Klose C, Bonventre J, Walz G, Kuehn E. A highly conserved tyrosine of Tim-3 is phosphorylated upon stimulation by its ligand galectin-9. Biochem Biophys Res Commun. 2006;351:571-6 pubmed..Given the role of TIM proteins in autoimmunity and cancer, the conserved SH2 binding domain surrounding Y265 could represent a possible target site for pharmacological intervention. ..
- Wang J, Shi L, Ma C, Ji X, Ying R, Wu X, et al. Differential regulation of interleukin-12 (IL-12)/IL-23 by Tim-3 drives T(H)17 cell development during hepatitis C virus infection. J Virol. 2013;87:4372-83 pubmed publisher..Our findings suggest that Tim-3-mediated differential regulation of IL-12/IL-23 drives T(H)17 cell development, a milieu favoring viral persistence and autoimmune phenomenon during HCV infection. ..
- Page N, Jones G, Stewart G. Genetic association studies between the T cell immunoglobulin mucin (TIM) gene locus and childhood atopic dermatitis. Int Arch Allergy Immunol. 2006;141:331-6 pubmed..In addition to confirming the importance of genetic variation in TIM-1, our results also suggest that genetic variants in the ligand for TIM-1, TIM-4, also contribute to the presentation of AD and related disorders. ..
- Yan J, Zhang Y, Zhang J, Liang J, Li L, Zheng L. Tim-3 expression defines regulatory T cells in human tumors. PLoS ONE. 2013;8:e58006 pubmed publisher..Together, our data indicate that Tim-3-expressing CD4 T cells in human tumors could represent the functional regulatory T cells which contribute to the formation of the immune-suppressive tumor micromilieu. ..
- Chae S, Park Y, Lee Y, Lee J, Chung H. The association of TIM-3 gene polymorphism with atopic disease in Korean population. Hum Immunol. 2004;65:1427-31 pubmed..029) was also significantly different. 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. ..
- Finney C, Ayi K, Wasmuth J, Sheth P, Kaul R, Loutfy M, et al. HIV infection deregulates Tim-3 expression on innate cells: combination antiretroviral therapy results in partial restoration. J Acquir Immune Defic Syndr. 2013;63:161-7 pubmed publisher..Our findings suggest that Tim-3 is differentially regulated on innate immune effector cells, and have direct implications for strategies designed to block Tim-3-ligand interactions. ..
- Fourcade J, Sun Z, Benallaoua M, Guillaume P, Luescher I, Sander C, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med. 2010;207:2175-86 pubmed publisher..Collectively, our findings support the use of Tim-3-Tim-3L blockade together with PD-1-PD-L1 blockade to reverse tumor-induced T cell exhaustion/dysfunction in patients with advanced melanoma. ..
- Ju Y, Hou N, Meng J, Wang X, Zhang X, Zhao D, et al. T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B. J Hepatol. 2010;52:322-9 pubmed publisher..HBV infection can up-regulate Tim-3 expression in NK cells, which may in turn suppress NK-cell functions in CHB patients. ..
- Han S, Feng S, Xu L, Shi W, Wang X, Wang H, et al. Tim-3 on peripheral CD4? and CD8? T cells is involved in the development of glioma. DNA Cell Biol. 2014;33:245-50 pubmed publisher..005) or Tim-3?CD8? T cells (p<0.001) in glioma patients. Our results suggested that Tim-3 may be involved in the development of glioma...
- Monney L, Sabatos C, Gaglia J, Ryu A, Waldner H, Chernova T, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 2002;415:536-41 pubmed..Tim-3 may have an important role in the induction of autoimmune diseases by regulating macrophage activation and/or function. ..
- McIntire J, Umetsu S, Akbari O, Potter M, Kuchroo V, Barsh G, et al. Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family. Nat Immunol. 2001;2:1109-16 pubmed..The human homolog of TIM-1 is the hepatitis A virus (HAV) receptor, which may explain the inverse relationship between HAV infection and the development of atopy. ..
- Liberal R, Grant C, Holder B, Ma Y, Mieli Vergani G, Vergani D, et al. The impaired immune regulation of autoimmune hepatitis is linked to a defective galectin-9/tim-3 pathway. Hepatology. 2012;56:677-86 pubmed publisher..Reduced levels of Tim-3 on CD4(pos) CD25(neg) effector cells and of Gal9 in T-regs contribute to impaired immunoregulation in AIH by rendering effector cells less prone to T-reg control and T-regs less capable of suppressing. ..
- Sanchez Fueyo A, Tian J, Picarella D, Domenig C, Zheng X, Sabatos C, et al. Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat Immunol. 2003;4:1093-101 pubmed..Our data indicate that the Tim-3 pathway provides an important mechanism to down-regulate T(H)1-dependent immune responses and to facilitate the development of immunological tolerance. ..
- Chae S, Park Y, Shim S, Yoon K, Chung H. The polymorphisms of Th1 cell surface gene Tim-3 are associated in a Korean population with rheumatoid arthritis. Immunol Lett. 2004;95:91-5 pubmed..001 ands 0.003, respectively) between RA patients and non-RA controls were significantly different. These results strongly suggest that -574T>G and 4259G>T polymorphism of the Tim-3 might be associated with susceptibility to RA. ..
- Gleason M, Lenvik T, McCullar V, Felices M, O Brien M, COOLEY S, et al. Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9. Blood. 2012;119:3064-72 pubmed publisher..In conclusion, we show that Tim-3 functions as a human NK-cell coreceptor to enhance IFN-? production, which has important implications for control of infectious disease and cancer. ..
- Jones R, Ndhlovu L, Barbour J, Sheth P, Jha A, Long B, et al. Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection. J Exp Med. 2008;205:2763-79 pubmed publisher..Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1-specific T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1-associated T cell dysfunction. ..
- Gao P, Mathias R, Plunkett B, Togias A, Barnes K, Beaty T, et al. Genetic variants of the T-cell immunoglobulin mucin 1 but not the T-cell immunoglobulin mucin 3 gene are associated with asthma in an African American population. J Allergy Clin Immunol. 2005;115:982-8 pubmed..Our findings suggest that the genetic variants of the TIM-1 but not the TIM-3 gene contribute to asthma susceptibility in this African-American population. ..
- Sabatos C, Chakravarti S, Cha E, Schubart A, Sanchez Fueyo A, Zheng X, et al. Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance. Nat Immunol. 2003;4:1102-10 pubmed..These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector T(H)1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance. ..
- Graves P, Siroux V, Guerra S, Klimecki W, Martinez F. Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain-IL-2-inducible T-cell kinase gene cluster in chromosome 5 q 33. J Allergy Clin Immunol. 2005;116:650-6 pubmed..45], P=.005; and 1.43 [1.01--2.01], P=.004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM 3 were significantly related to atopy and eczema...
- Zhu C, Anderson A, Schubart A, Xiong H, Imitola J, Khoury S, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6:1245-52 pubmed..These data suggest that the Tim-3-galectin-9 pathway may have evolved to ensure effective termination of effector T(H)1 cells. ..
- Miko E, Szereday L, Barakonyi A, Jarkovich A, Varga P, Szekeres Bartho J. Immunoactivation in preeclampsia: Vdelta2+ and regulatory T cells during the inflammatory stage of disease. J Reprod Immunol. 2009;80:100-8 pubmed publisher..In this study we report a series of observations, which taken together suggest the role of multiple pathways in generating an exaggerated systemic inflammatory response observed in the clinical stage of preeclampsia. ..
- Koguchi K, Anderson D, Yang L, O Connor K, Kuchroo V, Hafler D. Dysregulated T cell expression of TIM3 in multiple sclerosis. J Exp Med. 2006;203:1413-8 pubmed..MS) (n = 72) and four control subjects (n = 32) and assessed their cytokine profiles and expression levels of TIM3 and related molecules...
- Wiener Z, Kohalmi B, Pocza P, Jeager J, Tolgyesi G, Toth S, et al. TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells. J Invest Dermatol. 2007;127:906-14 pubmed..In conclusion, the immunoregulatory molecule TIM-3 in TGF-beta-stimulated mast cells and melanoma cells may support the survival of this tumor type. ..
- Yang L, Anderson D, Kuchroo J, Hafler D. Lack of TIM-3 immunoregulation in multiple sclerosis. J Immunol. 2008;180:4409-14 pubmed
- Li H, Wu K, Tao K, Chen L, Zheng Q, Lu X, et al. Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma. Hepatology. 2012;56:1342-51 pubmed publisher..Our work demonstrates that the Tim-3/galectin-9 signaling pathway mediates T-cell senescence in HBV-associated HCC. The data suggest that this pathway could be an immunotherapeutic target in patients with HBV-associated HCC. ..
- Meng Q, Liu Z, Rangelova E, Poiret T, Ambati A, Rane L, et al. Expansion of Tumor-reactive T Cells From Patients With Pancreatic Cancer. J Immunother. 2016;39:81-9 pubmed publisher..TIL composition was tested by CD45RA, CCR7, 4-1BB, LAG-3, PD-1, TIM3, and CTLA-4 marker analysis...
- Sweis R, Spranger S, Bao R, Paner G, Stadler W, Steinberg G, et al. Molecular Drivers of the Non-T-cell-Inflamed Tumor Microenvironment in Urothelial Bladder Cancer. Cancer Immunol Res. 2016;4:563-8 pubmed publisher..Upregulation of genes encoding immune checkpoint proteins PD-L1, IDO, FOXP3, TIM3, and LAG3 was associated with T-cell-inflamed tumors, suggesting potential for sensitivity to checkpoint blockade...
- Quan L, Lan X, Meng Y, Guo X, Guo Y, Zhao L, et al. BTLA marks a less cytotoxic T-cell subset in diffuse large B-cell lymphoma with high expression of checkpoints. Exp Hematol. 2018;60:47-56.e1 pubmed publisher..Taken together, our data provide the first evidence that increased BTLA predicts poor prognosis in patients with DLBCL, and blockade of BTLA with other checkpoints may potentially represent a new strategy for immunotherapy of DLBCL. ..
- Torphy R, Schulick R, Zhu Y. Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy. Int J Mol Sci. 2017;18: pubmed publisher..Herein, we will summarize our current progress and understanding of these newly-characterized immune checkpoints and their potential application in cancer immunotherapy. ..
- Wang J, Sun F, Lin X, Li Z, Mao X, Jiang C. Cytotoxic T cell responses to Streptococcus are associated with improved prognosis of oral squamous cell carcinoma. Exp Cell Res. 2018;362:203-208 pubmed publisher..salivarius-reactive and S. anginosus-reactive CD8 T cells. Together, we demonstrated that Streptococcus-reactive CD8 T cell responses might contribute to antitumor immunity in OSCC patients. ..
- Li X, Chen Y, Liu X, Zhang J, He X, Teng G, et al. Tim3/Gal9 interactions between T cells and monocytes result in an immunosuppressive feedback loop that inhibits Th1 responses in osteosarcoma patients. Int Immunopharmacol. 2017;44:153-159 pubmed publisherThe Tim3/Gal9 pathway is associated with immunosuppression and worse clinical outcome in multiple cancers...
- Zhang Y, Cai P, Li L, Shi L, Chang P, Liang T, et al. Co-expression of TIM-3 and CEACAM1 promotes T cell exhaustion in colorectal cancer patients. Int Immunopharmacol. 2017;43:210-218 pubmed publisher..We for the first time to our knowledge suggested that co-expression of TIM-3 and CEACAM1 can mediate T cell exhaustion and may be potential biomarkers for CRC prediction, highlighting the possibility of being immunotherapy targets. ..
- Fooladinezhad H, Khanahmad H, Ganjalikhani Hakemi M, Doosti A. Negative regulation of TIM-3 expression in AML cell line (HL-60) using miR-330-5p. Br J Biomed Sci. 2016;73:129-133 pubmed..According to our results, miR-330-5p has a strong inhibitory effect on TIM-3 expression in AML cell line. Thus, the bioinformatics prediction of Mirwalk and Target Scan softwares for silencing effect of miR-330-5p on TIM-3 is confirmed. ..
- Okoye I, Namdar A, Xu L, Crux N, Elahi S. Atorvastatin downregulates co-inhibitory receptor expression by targeting Ras-activated mTOR signalling. Oncotarget. 2017;8:98215-98232 pubmed publisher..Thus, our results suggest that statins may hold particular promise in reinvigorating T cell function in chronic conditions...
- Li L, Yang L, Wang L, Wang F, Zhang Z, Li J, et al. Impaired T cell function in malignant pleural effusion is caused by TGF-? derived predominantly from macrophages. Int J Cancer. 2016;139:2261-9 pubmed publisher..Our results indicate that macrophage-derived TGF-? plays an important role in impaired T cell cytotoxicity. It will therefore be valuable to develop therapeutic strategies against TGF-? pathway for MPE therapy of lung cancer. ..
- Heon E, Wulan H, Macdonald L, Malek A, Braunstein G, Eaves C, et al. IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer. Biochem Biophys Res Commun. 2015;464:360-6 pubmed publisher..Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion inÂ vitro, a crucial step in adoptive T cell therapy. ..
- Renesto P, Ponciano V, Cenedeze M, Saraiva Câmara N, Pacheco Silva A. High expression of Tim-3 mRNA in urinary cells from kidney transplant recipients with acute rejection. Am J Transplant. 2007;7:1661-5 pubmed..40 +/- 38.71), compared with No-AR (4.69 +/- 12.62), and stable transplants (0.38 +/- 0.44) p < 0.001. The highest expression of TIM-3 in AR makes it a promising noninvasive test for its diagnosis. ..