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自身免疫风险等位基因：B 细胞调控信号通路中的热点。

Autoimmunity risk alleles: hotspots in B cell regulatory signaling pathways.

机构信息

Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, Colorado, USA.

出版信息

J Clin Invest. 2013 May;123(5):1928-31. doi: 10.1172/JCI69289. Epub 2013 Apr 24.

DOI:10.1172/JCI69289
PMID:23619359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3635745/
Abstract

Autoimmunity is the consequence of the combination of genetic predisposition and environmental effects, such as infection, injury, and constitution of the gut microbiome. In this edition of the JCI, Dai et al. describe the use of knockin technology to test the mechanism of action of a polymorphism in the protein tyrosine phosphatase nonreceptor 22 (PTPN22) (LYP) that is associated with susceptibility to multiple autoimmune diseases. The function of this allele, and that of a disproportionate number of autoimmune disease risk alleles, suggests that inhibitory signaling pathways that maintain B lymphocyte immune tolerance may represent an Achilles' heel in the prevention of autoimmunity.

摘要

自身免疫是遗传易感性和环境影响（如感染、损伤和肠道微生物组组成）共同作用的结果。在这一期的 JCI 中，Dai 等人描述了使用基因敲入技术来测试与多种自身免疫性疾病易感性相关的蛋白酪氨酸磷酸酶非受体 22（PTPN22）（LYP）蛋白突变的作用机制。该等位基因的功能以及相当数量的自身免疫疾病风险等位基因的功能表明，维持 B 淋巴细胞免疫耐受的抑制信号通路可能代表预防自身免疫的阿喀琉斯之踵。

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本文引用的文献

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A disease-associated PTPN22 variant promotes systemic autoimmunity in murine models.一种与疾病相关的 PTPN22 变异体可在小鼠模型中促进全身性自身免疫。
J Clin Invest. 2013 May;123(5):2024-36. doi: 10.1172/JCI66963. Epub 2013 Apr 24.
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CSK regulatory polymorphism is associated with systemic lupus erythematosus and influences B-cell signaling and activation.CSK 调节多态性与系统性红斑狼疮有关，并影响 B 细胞信号转导和激活。
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Interaction of TAPP adapter proteins with phosphatidylinositol (3,4)-bisphosphate regulates B-cell activation and autoantibody production.TAPP 衔接蛋白与磷脂酰肌醇（3,4）-二磷酸的相互作用调节 B 细胞的激活和自身抗体的产生。
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The functions and regulation of the PTEN tumour suppressor.PTEN 肿瘤抑制因子的功能与调节。
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Central B-cell tolerance: where selection begins.中枢 B 细胞耐受：选择开始的地方。
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Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase-mediated inhibitory signaling cascade required for B cell anergy.CD79a 和 CD79b ITAM 基序的单磷酸化启动了需要 B 细胞失能的SHIP-1 磷酸酶介导的抑制性信号级联反应。
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Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK.B 细胞系统性红斑狼疮相关基因 BANK1 和 BLK 的遗传和物理相互作用。
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The autoimmune disease-associated PTPN22 variant promotes calpain-mediated Lyp/Pep degradation associated with lymphocyte and dendritic cell hyperresponsiveness.自身免疫性疾病相关的 PTPN22 变体促进钙蛋白酶介导的 Lyp/Pep 降解，与淋巴细胞和树突状细胞的高反应性相关。
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Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes.在一个大型病例对照研究集中的系统性红斑狼疮风险等位基因，以及与临床亚表型的关联。
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