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Nature:BACH2的抗炎作用

来源:Nature 2013-07-03 15:17

编码转录因子BACH2的一个位点内的多态性,与包括哮喘、多发性硬化、克罗恩氏病、腹腔病和1-型糖尿病在内的若干种过敏和自体免疫疾病相关。这篇论文识别出了BACH2可能用来帮助自体免疫的一个机制。Roychoudhuri等人解释了BACH2是怎样通过稳定调控性T-细胞的分化来抑制其他细胞命运从而限制自体免疫的。这些发现说明,BACH2起CD4+ T-细胞分化的一个调控因子的作用,通过控制耐受与免疫之间的平衡来防止炎症。(生物谷Bioon.com)

生物谷推荐英文摘要:

Nature    doi:10.1038/nature12199

BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis

Rahul Roychoudhuri,  Kiyoshi Hirahara,Kambiz Mousavi, David Clever,Christopher A. Klebanoff,Michael Bonelli,Giuseppe Sciumè,Hossein Zare,Golnaz Vahedi,Barbara Dema,Zhiya Yu,Hui Liu,Hayato Takahashi,Mahadev Rao,Pawel Muranski,Joseph G.Crompton,George Punkosdy,Davide Bedognetti,Ena Wang,Victoria Hoffmann,Juan Rivera,Francesco M. Marincola,Atsushi Nakamura,Vittorio Sartorelli,Yuka Kanno et al.

Through their functional diversification, distinct lineages of CD4+ T cells can act to either drive or constrain immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment. Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseases including asthma, Crohn’s disease, coeliac disease, vitiligo, multiple sclerosis and type 1 diabetes. Although these associations point to a shared mechanism underlying susceptibility to diverse immune-mediated diseases, a function for BACH2 in the maintenance of immune homeostasis has not been established. Here, by studying mice in which the Bach2 gene is disrupted, we define BACH2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programs of multiple effector lineages in CD4+ T cells. BACH2 was required for efficient formation of regulatory (Treg) cells and consequently for suppression of lethal inflammation in a manner that was Treg-cell-dependent. Assessment of the genome-wide function of BACH2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during Treg polarization resulted in inappropriate diversion to effector lineages. In addition, BACH2 constrained full effector differentiation within TH1, TH2 and TH17 cell lineages. These findings identify BACH2 as a key regulator of CD4+ T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity.

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