Dianzani Umberto, Chiocchetti Annalisa, Ramenghi Ugo
Interdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Medical Sciences, "A. Avogadro" University of Eastern Piedmont, Via Solaroli 17, 28100, Novara, Italy.
Life Sci. 2003 May 9;72(25):2803-24. doi: 10.1016/s0024-3205(03)00196-6.
Fas is a death receptor belonging to the TNFR superfamily and induces cell apoptosis by both activating a caspase cascade and altering mitochondria. In the immune system, Fas is involved in the switching-off of the immune responses and cell mediated cytotoxicity. In humans, genetic defects decreasing Fas function cause the Autoimmune Lymphoproliferative Syndrome (ALPS) where autoimmunities are associated with accumulation of polyclonal lymphocytes in the secondary lymphoid tissues and expansion of T cells lacking both CD4 and CD8 (DN cells). Expansion of DN cells is absent in an ALPS variant, named Dianzani's Autoimmune Lymphoproliferative Disease (DALD). The observation that DALD patients' families display increased frequency of autoimmune diseases different from ALPS suggests that defects of Fas function may also play a role in development of "common" autoimmune diseases. This possibility is supported by detection of defective Fas function in substantial proportions of patients with the multiple autoimmune syndrome or aggressive forms of type 1 diabetes or multiple sclerosis. This article reviews data suggesting that development of autoimmune/lymphoproliferative patterns may involve several alterations hitting the Fas system, but might also involve alterations in other systems contributing to the switching-off or proliferation of lymphocytes.
Fas是一种属于肿瘤坏死因子受体（TNFR）超家族的死亡受体，通过激活半胱天冬酶级联反应和改变线粒体来诱导细胞凋亡。在免疫系统中，Fas参与免疫反应的终止和细胞介导的细胞毒性作用。在人类中，Fas功能降低的遗传缺陷会导致自身免疫性淋巴增生综合征（ALPS），其中自身免疫与次级淋巴组织中多克隆淋巴细胞的积累以及缺乏CD4和CD8的T细胞（双阴性细胞，DN细胞）的扩增有关。在一种名为迪亚扎尼自身免疫性淋巴增生性疾病（DALD）的ALPS变体中不存在DN细胞的扩增。DALD患者家族中出现不同于ALPS的自身免疫性疾病频率增加的观察结果表明，Fas功能缺陷也可能在“常见”自身免疫性疾病的发生中起作用。多发性自身免疫综合征、侵袭性1型糖尿病或多发性硬化症患者中相当比例检测到Fas功能缺陷支持了这种可能性。本文综述了相关数据，表明自身免疫/淋巴增生模式的发生可能涉及影响Fas系统的多种改变，但也可能涉及其他有助于淋巴细胞终止或增殖的系统的改变。
