2012年9月8日 讯 /生物谷BIOON/ --近日，来自澳大利亚沃尔特与伊丽莎医学研究所的研究者发现了一对分子可以共同发挥作用来杀灭称为自我反应的免疫细胞（'self-reactive' immune cells），自我反应的免疫细胞可以攻击机体自身的组织和器官。这项研究发现刊登于近日的国际杂志Immunity上，或许可以帮助我们解释自身免疫疾病的发病机理。
自身免疫疾病（Autoimmune diseases），如I型糖尿病、风湿性关节炎、炎性肠病和多发性硬化症，都与由于免疫细胞像机体自身发动攻击所致，这将破坏机体的器官或者其结构功能。Puma和Bim是所谓的BH3仅有蛋白质（BH3-only protein），其可以通过细胞凋亡使细胞死亡，细胞凋亡蛋白质的缺失可以引发很多疾病，包括癌症和神经变性疾病。
研究者Gay教授表示，目前只有迫使大部分的自身免疫细胞在发育过程中死亡，才能够抵御自身免疫疾病的发病。如果自身免疫细胞成熟的话，机体就会开启第二道防线来使得这些危险细胞处于沉默状态，以阻止其产生自身免疫疾病。
Gray说道，我们如今知道自身免疫细胞死亡时应对自身免疫疾病最好的保护方法，下一步我们的研究工作就是发现，伴随其它因子所导致的细胞死亡是否会引发机体自身免疫疾病的发生。（生物谷Bioon.com）
编译自：Immune cell death safeguards against autoimmune disease
doi:10.1016/j.immuni.2012.05.030
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The BH3-Only Proteins Bim and Puma Cooperate to Impose Deletional Tolerance of Organ-Specific Antigens
Daniel H.D. Gray, Fiona Kupresanin, Stuart P. Berzins, Marco J. Herold, Lorraine A. O'Reilly, Philippe Bouillet, Andreas Strasser
Although the proapoptotic BH3-only protein, Bim, is required for deletion of autoreactive thymocytes, Bim-deficient mice do not succumb to extensive organ-specific autoimmune disease. To determine whether other BH3-only proteins safeguard tolerance in the absence of Bim, we screened mice lacking Bim as well as other BH3-only proteins. Most strains showed no additional defects; however, mice deficient for both Puma and Bim spontaneously developed autoimmunity in multiple organs, and their T cells could transfer organ-specific autoimmunity. Puma- and Bim-double-deficient mice had a striking accumulation of mature, single-positive thymocytes, suggesting an additional defect in thymic deletion was the basis for disease. Transgenic mouse models of thymocyte deletion by peripheral neoantigens confirmed that the loss of Bim and Puma allowed increased numbers of autoreactive thymocytes to escape deletion. Our data show that Puma cooperates with Bim to impose a thymic-deletion checkpoint to peripheral self-antigens and cement the notion that defects in apoptosis alone are sufficient to cause autoimmune disease.
