.png){kind=icon}
返回
The TIGIT/CD226 Axis Regulates Human T Cell Function
.png){kind=icon}
OA
AI
DOI：10.4049/jimmunol.1103627.png)
.png){kind=icon}
.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
T cell Ig and ITIM domain (TIGIT) is a newly identified receptor expressed on T cells that binds to CD155 on the dendritic cell surface, driving them to a more tolerogenic phenotype. Given that TIGIT contains an ITIM motif in its intracellular domain and considering the potential importance of the TIGIT/CD226 pathway in human autoimmune disease, we investigated the specific role of TIGIT in human CD4(+) T cells. Using an agonistic anti-TIGIT mAb, we demonstrate a direct inhibitory effect on T cell proliferation with a decrease in expression of T-bet, GATA3, IFN regulatory factor 4, and retinoic acid-related orphan receptor c with inhibition of cytokine production, predominantly IFN-gamma. Knockdown of TIGIT expression by short hairpin RNA resulted in an increase of both T-bet and IFN-gamma mRNA and protein expression with concomitant decrease in IL-10 expression. Increases in IFN-gamma with TIGIT knockdown could be overcome by blocking CD226 signaling, indicating that TIGIT exerts immunosuppressive effects by competing with CD226 for the same CD155 ligand. These data demonstrate that TIGIT can inhibit T cell functions by competing with CD226 and can also directly inhibit T cells in a T cell-intrinsic manner. Our results provide evidence for a novel role of this alternative costimulatory pathway in regulating human T cell responses associated with autoimmune disease. The Journal of Immunology, 2012, 188: 3869-3875.
Keyword:
MULTIPLE-SCLEROSIS
AUTOIMMUNE-DISEASE
PVR CD155
DNAM-1
LIGANDS
COSTIMULATION
ASSOCIATION
MECHANISMS
MOLECULE
RECEPTOR
AI总结
对已上传原文的论文进行重点信息的提取，主要内容包括：简要概述、研究摘要、背景介绍、关键亮点、图文解析、展望与总结。
期刊
IF:
3.4
论文数:
3.7W
被引数:
9.9W
机构
引用论文
分享收藏The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells表面蛋白TIGIT通过促进成熟的免疫调节性树突状细胞的生成来抑制T细胞活化.png)
NATURE IMMUNOLOGY
NATURE IMMUNOLOGYIF27.6
PREAI
分享收藏The expanding genetic overlap between multiple sclerosis and type I diabetesGENES AND IMMUNITYOAAI
GENES AND IMMUNITYIF4.5
OAAI分享收藏An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells缺乏B7结合域信号的自身免疫性疾病相关CTLA-4剪接变体在T细胞中呈阴性IMMUNITYOAAI
IMMUNITYIF26.3
OAAI分享收藏
分享收藏
查看更多内容