An autoimmune disease risk SNP, rs2281808, in SIRPG is associated with reduced expression of SIRPγ and heightened effector state in human CD8 T-cells.
An autoimmune disease risk SNP, rs2281808, in SIRPG is associated with reduced expression of SIRPγ and heightened effector state in human CD8 T-cells.
复制标题
DOI：
10.1038/s41598-018-33901-1
复制
发表时间：
2018-10-18
影响因子：
4.6
通讯作者：
Karandikar NJ
中科院分区：
文献类型：
--
作者：
Sinha S;Borcherding N;Renavikar PS;Crawford MP;Tsalikian E;Tansey M;Shivapour ET;Bittner F;Kamholz J;Olalde H;Gibson E;Karandikar NJ
多项全基因组关联研究（GWAS）表明，存在于SIRPG基因内的单核苷酸多态性（SNP）rs2281808的TT变异与自身免疫性疾病相关，比如1型糖尿病。然而，SIRPγ在人类T细胞中的作用尚不明确，TT变异的功能意义也不清楚。在此我们研究了SIRPG基因型及其对人类T细胞命运和功能的影响。我们发现T变异的存在导致T细胞上SIRPγ表达降低。在功能上，CT和TT个体中SIRPγ低表达的CD8 T细胞处于一种效应增强状态，激活阈值更低，并且与迁移和细胞毒性潜能相关的基因和分子表达更高。此外，SIRPγ低表达的CD8 T细胞缺乏与长期功能性记忆形成相关的转录因子。我们的研究揭示了SNP rs2281808的生物学影响，并为SIRPγ可能调节人类免疫应答的潜在机制提供了新的见解。
Multiple GWAS studies have shown that the SNP rs2281808 TT variant, present within the SIRPG gene, is associated with autoimmune diseases, such as type 1 diabetes. However, the role of SIRPγ in human T-cells is not known, neither is the functional significance of TT variant. Here we investigated SIRPG genotypes and their effects on the fate and function of human T-cells. We found that the presence of T variant resulted in reduction of SIRPγ expression on T-cells. Functionally, SIRPγlow CD8 T-cells in CT and TT individuals existed in a heightened effector state with lower activation threshold and had greater expression of genes and molecules associated with migratory and cytotoxic potential. Further, SIRPγlow CD8 T-cells were deficient in transcription factors associated with long-term functional memory formation. Our study reveals biological consequences of the SNP rs2281808 and provides novel insights into the potential mechanisms by which SIRPγ might regulate human immune responses.
登录
查看更多内容
影响因子：
11
作者：
Fu SH;Yeh LT;Chu CC;Yen BL;Sytwu HK
通讯作者：
Sytwu HK
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
5
作者：
Reddy, M. V. Prasad Linga;Wang, H.;Liu, S.;Bode, B.;Reed, J. C.;Steed, R. D.;Anderson, S. W.;Steed, L.;Hopkins, D.;She, J-X
通讯作者：
She, J-X
影响因子：
--
作者：
Soneson C;Love MI;Robinson MD
通讯作者：
Robinson MD
影响因子：
3.7
作者：
Chowdhury FZ;Estrada LD;Murray S;Forman J;Farrar JD
通讯作者：
Farrar JD