T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status

Song, Yeong Wook; Im, Churl Hyun; Park, Jae Hee; Lee, Yun Jong; Lee, Eun Young; Park, Kyung-Sook

doi:10.1016/j.humimm.2011.04.007

Cited by 21 publications

(12 citation statements)

References 23 publications

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“…TIM-3 −574G/T and +4259T/G were identified in patients with HIV-related non-Hodgkin lymphoma, non-small-cell lung cancer, and pancreatic cancer [20, 21, 36]. Rs11742259, rs10515746, rs35690726 and rs1036199 in TIM-3 were significantly associated with rheumatoid arthritis [37]. However, there were no previous reports of a relationship between TIM-3 polymorphisms and the risk of BC.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study

et al. 2016

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Previous studies have found associations between polymorphisms in T cell immunoglobulin and mucin domain 3 (TIM-3) and increased risks of various cancers. However, the association between TIM-3 polymorphisms and breast cancer (BC) remains uncertain. In this study, a total of 560 BC patients and 583 age, sex, and ethnicity-matched healthy controls from Northwest China were included. The polymorphisms were genotyped using Sequenom MassARRAY. The expression level of TIM-3 protein was detected by immunohistochemistry. We observed rs10053538 had a significantly increased risk of BC, comparing with the wild-type genotype even after Bonferroni correction. In addition, the rs4704853 G>A variants were more frequent among BC patients than the controls (GA + AA vs. GG: OR = 1.32, 95% CI = 1.03-1.69, P = 0.026); However, the significance was lost after Bonferroni correction (P = 0.078). Furthermore, rs10053538 was associated with lymph node metastasis. Age stratification revealed that among patients aged <49 years, those with the rs4704853 GA/AA genotype had a higher risk of BC; But there was no difference when Bonferroni correction was conducted. Immunohistochemical analysis showed that the expression of TIM-3 protein in the breast cancer tissues was higher in patients carrying the rs10053538 GT+TT genotype than those with GG genotype (P = 0.012). However, we failed to find any difference between BC patients and controls in any rs1036199 genetic model. These findings suggested that rs10053538 in TIM-3 might increase susceptibility to BC and promote the progression of BC in Chinese women.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study

et al. 2016

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“…Indeed, co-inhibitory receptors play a central role in maintaining immune homeostasis and their loss, most notably of CTLA-4 or PD-1, results in spontaneous, severe autoimmunity with loss of CTLA-4 and a milder form of tissue inflammation with loss of PD-1 (Tivol et al 1995; Waterhouse et al 1995; Nishimura et al 1999; Nishimura et al 2001). Many co-inhibitory pathways, including the Tim-3 and CD226/TIGIT pathways, have been genetically linked to susceptibility to autoimmune diseases and their function in regulating immune responses has been intensively studied in the context of autoimmune diseases (Kasagi et al 2011; Qu et al 2009; Wang et al 2014; Song et al 2011; Hafler et al 2009). However, deficiency in Tim-3, Lag-3, or TIGIT alone does not predispose to autoimmunity unless the mice are on a permissive background (Joller et al 2011; Bettini et al 2011; Okazaki et al 2011; Lee and Goverman 2013).…”

Section: Role In Diseases and Therapymentioning

confidence: 99%

Tim-3, Lag-3, and TIGIT

Joller

Kuchroo

2017

Current Topics in Microbiology and Immunology

119

106

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Co-inhibitory receptors play a key role in regulating T cell responses and maintaining immune homeostasis. Their inhibitory function prevents autoimmune responses but also restricts the ability of T cells to mount effective immune responses against tumors or persistent pathogens. T cells express a module of co-inhibitory receptors, which display great diversity in expression, structure, and function. Here, we focus on the co-inhibitory receptors Tim-3, Lag-3, and TIGIT and how they regulate T cell function, maintenance of self-tolerance, their role in regulating ongoing T cell responses at peripheral tissues, and their synergistic effects in regulating autoimmunity and antitumor responses.

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“…Co-inhibitory receptors play a central role in regulating autoimmune disease. Indeed, many co-inhibitory receptors have been genetically linked to autoimmune diseases (Kasagi et al, 2011; Qu et al, 2009; Song et al, 2011; Wang et al, 2014). [Au: Would like to call out the Vignali review on this topic in this issue here?…”

Section: Introductionmentioning

confidence: 99%

Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation

2016

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Summary Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co-inhibitory receptor expression on T cells dampens effector T cell responses. Unfortunately, many patients still fail to respond to therapies that target CTLA-4 and PD-1. The next wave of co-inhibitory receptor targets that are being explored in clinical trials include Lag-3, Tim-3, and TIGIT. These receptors while belonging to the same class of receptors as PD-1 and CTLA-4 exhibit unique functions especially at tissue sites where they regulate distinct aspects of immunity. Increased understanding of the specialized functions of these receptors will inform the rational application of therapies that target these receptors to the clinic.

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T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status

Cited by 21 publications

References 23 publications

Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study

Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study

Tim-3, Lag-3, and TIGIT

Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation

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