SH2D1A regulates T-dependent humoral autoimmunity.

SH2D1A regulates T-dependent humoral autoimmunity.
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DOI:
10.1084/jem.20040526
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发表时间:
2004-07-19
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Peng SL
Peng SL
中科院分区:
其他
文献类型:
--
作者:
Hron JD;Caplan L;Gerth AJ;Schwartzberg PL;Peng SL

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信号淋巴细胞激活分子(SLAM)/CD150家族包含一组由1号染色体编码的细胞表面分子,其共刺激功能部分由衔接蛋白SH2D1A(SLAM相关蛋白,SAP)介导。SH2D1A的缺乏可使小鼠免受狼疮实验模型的影响,包括高丙种球蛋白血症、包括抗双链DNA在内的自身抗体以及肾脏疾病的发生。这种保护作用并不反映T细胞或B细胞本身功能存在严重缺陷,因为SH2D1A缺陷小鼠易患实验性自身免疫性脑脊髓炎(一种T细胞依赖性疾病),并且它们能够产生正常的T细胞非依赖性抗原特异性免疫球蛋白反应。相反,SH2D1A缺陷小鼠的T细胞依赖性抗体反应受损,这反映了生发中心形成存在缺陷。这些发现表明SLAM - SH2D1A系统在调节T细胞依赖性体液免疫反应中具有特定作用,这意味着CD150 - SH2D1A家族成员是抗体介导的自身免疫性和过敏性疾病发病机制及治疗的靶点。
The signaling lymphocytic activation molecule (SLAM)/CD150 family includes a family of chromosome 1–encoded cell surface molecules with costimulatory functions mediated in part by the adaptor protein SH2D1A (SLAM-associated protein, SAP). Deficiency in SH2D1A protects mice from an experimental model of lupus, including the development of hypergammaglobulinemia, autoantibodies including anti–double stranded DNA, and renal disease. This protection did not reflect grossly defective T or B cell function per se because SH2D1A-deficient mice were susceptible to experimental autoimmune encephalomyelitis, a T cell–dependent disease, and they were capable of mounting normal T-independent antigen-specific immunoglobulin responses. Instead, T-dependent antibody responses were impaired in SH2D1A-deficient mice, reflecting defective germinal center formation. These findings demonstrate a specific role for the SLAM–SH2D1A system in the regulation of T-dependent humoral immune responses, implicating members of the CD150–SH2D1A family as targets in the pathogenesis and therapy of antibody-mediated autoimmune and allergic diseases.
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