Wang J, Zheng L, Lobito A, Chan F K, Dale J, Sneller M, Yao X, Puck J M, Straus S E, Lenardo M J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cell. 1999 Jul 9;98(1):47-58. doi: 10.1016/S0092-8674(00)80605-4.
Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects, that harbor independent missense mutations in Caspase 10. These encode amino acid substitutions that decrease caspase activity and interfere with death receptor-induced apoptosis, particularly that stimulated by Fas ligand and TRAIL. These results provide evidence that inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II.
半胱天冬酶是一类半胱氨酸蛋白酶，在系统发育上多样的多细胞生物体中介导程序性细胞死亡。我们在此报告了两个患有II型自身免疫性淋巴细胞增生综合征（ALPS）的家族，其特征为淋巴细胞和树突状细胞内环境稳定异常以及免疫调节缺陷，这两个家族在半胱天冬酶10中存在独立的错义突变。这些突变编码的氨基酸替代会降低半胱天冬酶活性，并干扰死亡受体诱导的细胞凋亡，尤其是由Fas配体和TRAIL刺激引起的凋亡。这些结果证明，遗传性非致死性半胱天冬酶异常会导致II型ALPS自身免疫基础上的多效性凋亡缺陷。
