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(xué)研究所的研究者發(fā)現(xiàn)了一對(duì)分子可以共同發(fā)揮作用來殺滅稱為自我反應(yīng)的免疫細(xì)胞（'self-reactive' immune cells）,，自我反應(yīng)的免疫細(xì)胞可以攻擊機(jī)體自身的組織和器官,。這項(xiàng)研究發(fā)現(xiàn)刊登于近日的國(guó)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(jī)理。
自身免疫疾?。ˋutoimmune diseases）,，如I型糖尿病、風(fēng)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(xì)胞像機(jī)體自身發(fā)動(dòng)攻擊所致，這將破壞機(jī)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(xì)胞凋亡使細(xì)胞死亡，細(xì)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(xì)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(xì)胞成熟的話，機(jī)體就會(huì)開啟第二道防線來使得這些危險(xiǎn)細(xì)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?xì)胞死亡時(shí)應(yīng)對(duì)自身免疫疾病最好的保護(hù)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(dǎo)致的細(xì)胞死亡是否會(huì)引發(fā)機(jī)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
PMC:
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.
