2012年9月8日 訊 /生物谷BIOON/ --近日，來自澳大利亞沃爾特與伊麗莎醫(yī)學研究所的研究者發(fā)現(xiàn)了一對分子可以共同發(fā)揮作用來殺滅稱為自我反應的免疫細胞（'self-reactive' immune cells）,，自我反應的免疫細胞可以攻擊機體自身的組織和器官,。這項研究發(fā)現(xiàn)刊登于近日的國際雜志Immunity上,，或許可以幫助我們解釋自身免疫疾病的發(fā)病機理。
自身免疫疾?。ˋutoimmune diseases）,，如I型糖尿病、風濕性關(guān)節(jié)炎,、炎性腸病和多發(fā)性硬化癥,，都與由于免疫細胞像機體自身發(fā)動攻擊所致，這將破壞機體的器官或者其結(jié)構(gòu)功能,。Puma和Bim是所謂的BH3僅有蛋白質(zhì)（BH3-only protein）,，其可以通過細胞凋亡使細胞死亡，細胞凋亡蛋白質(zhì)的缺失可以引發(fā)很多疾病,，包括癌癥和神經(jīng)變性疾病,。
研究者Gay教授表示，目前只有迫使大部分的自身免疫細胞在發(fā)育過程中死亡,，才能夠抵御自身免疫疾病的發(fā)病,。如果自身免疫細胞成熟的話,，機體就會開啟第二道防線來使得這些危險細胞處于沉默狀態(tài)，以阻止其產(chǎn)生自身免疫疾病,。
Gray說道,，我們?nèi)缃裰雷陨砻庖呒毎劳鰰r應對自身免疫疾病最好的保護方法，下一步我們的研究工作就是發(fā)現(xiàn),，伴隨其它因子所導致的細胞死亡是否會引發(fā)機體自身免疫疾病的發(fā)生,。（生物谷Bioon.com）
編譯自：Immune cell death safeguards against autoimmune disease
doi:10.1016/j.immuni.2012.05.030
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PMID:
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.
