Genetic basis of defects in immune tolerance underlying the development of autoimmunity.
Genetic basis of defects in immune tolerance underlying the development of autoimmunity.
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DOI：
10.3389/fimmu.2022.972121
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
与自身免疫性疾病易感性相关的遗传变异为免疫耐受丧失和随后自身抗体、组织损伤和临床疾病发作的机制提供了重要的见解。在这里，我们回顾了在多种自身免疫性疾病中共享的遗传变异如何有助于我们对全球耐受失败的理解，重点是人类白细胞抗原区域PTPN 2和PTPN 22的变异，以及它们在抗原呈递和T和B细胞稳态中的作用。还讨论了特定自身免疫性疾病特有的变体，如与类风湿性关节炎相关的PADI 2和PADI 4中的变体，并讨论了它们在疾病特异性免疫病理学中的作用。目前的研究继续集中在确定自身免疫性疾病相关变体的功能后果，但最近已扩展到基因组非编码区的变体，使用新的方法来研究这些变体对调节基因表达机制的影响。最后，研究自身免疫性疾病中的遗传风险变异具有临床意义，有助于预测谁会患上自身免疫性疾病，并确定潜在的治疗靶点。
Genetic variants associated with susceptibility to autoimmune disease have provided important insight into the mechanisms responsible for the loss of immune tolerance and the subsequent development of autoantibodies, tissue damage, and onset of clinical disease. Here, we review how genetic variants shared across multiple autoimmune diseases have contributed to our understanding of global tolerance failure, focusing on variants in the human leukocyte antigen region, PTPN2 and PTPN22, and their role in antigen presentation and T and B cell homeostasis. Variants unique to a specific autoimmune disease such as those in PADI2 and PADI4 that are associated with rheumatoid arthritis are also discussed, addressing their role in disease-specific immunopathology. Current research continues to focus on determining the functional consequences of autoimmune disease-associated variants but has recently expanded to variants in the non-coding regions of the genome using novel approaches to investigate the impact of these variants on mechanisms regulating gene expression. Lastly, studying genetic risk variants in the setting of autoimmunity has clinical implications, helping predict who will develop autoimmune disease and also identifying potential therapeutic targets.
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DOI：
10.1084/jem.20100239
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li P;Li M;Lindberg MR;Kennett MJ;Xiong N;Wang Y
通讯作者：
Wang Y
影响因子：
2.6
作者：
Gough SC;Simmonds MJ
通讯作者：
Simmonds MJ
影响因子：
13.3
作者：
Honda, Suguru;Ikari, Katsunori;Kochi, Yuta
通讯作者：
Kochi, Yuta
DOI：
10.1056/nejmra1911109
发表时间：
2020-09-17
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bluestone JA;Anderson M
通讯作者：
Anderson M
影响因子：
30.8
作者：
Fortune MD;Guo H;Burren O;Schofield E;Walker NM;Ban M;Sawcer SJ;Bowes J;Worthington J;Barton A;Eyre S;Todd JA;Wallace C
通讯作者：
Wallace C