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Cdh4调控自身抗原表达来增强中枢免疫耐受
2020-06-30 21:40

近日,日本东京大学Hiroshi Takayanagi课题组发现,Cdh4调控自身抗原表达来增强中枢免疫耐受。该项研究成果于2020年6月29日在线发表在《自然—免疫学》杂志上。

研究人员发现染色质重塑因子Chd4(也称为Mi-2β)在髓样胸腺上皮细胞的自身抗原表达中起关键作用。为了使自身抗原表达的多样性最大化,Fezf2和Aire利用了完全不同的转录机制,这两种机制都在Chd4的控制下。

Chd4组织了Fezf2依赖基因的启动子区域,同时通过超级增强子有助于Aire介导的自身抗原诱导。胸腺上皮细胞中特异性缺乏Chd4的小鼠表现出自身免疫表型,包括T细胞浸润。因此,Chd4在整合Fezf2和Aire介导的基因诱导并建立中枢免疫耐受中起到了关键作用。

据悉,胸腺中自身反应性T细胞被消除,从而通过在胸腺髓样上皮细胞中组织限制性自身抗原的混杂表达来防止自身免疫。这种表达依赖于转录因子Fezf2以及转录调节因子Aire,但是转录程序的整个情况却不清楚。

附:英文原文

Title: Chd4 choreographs self-antigen expression for central immune tolerance

Author: Yoshihiko Tomofuji, Hiroyuki Takaba, Hiroshi I. Suzuki, Rayene Benlaribi, Cristian David Pea Martinez, Yoshihiro Abe, Yasuyuki Morishita, Tadashi Okamura, Akashi Taguchi, Tatsuhiko Kodama, Hiroshi Takayanagi

Issue&Volume: 2020-06-29

Abstract: Autoreactive T cells are eliminated in the thymus to prevent autoimmunity by promiscuous expression of tissue-restricted self-antigens in medullary thymic epithelial cells. This expression is dependent on the transcription factor Fezf2, as well as the transcriptional regulator Aire, but the entire picture of the transcriptional program has been obscure. Here, we found that the chromatin remodeler Chd4, also called Mi-2β, plays a key role in the self-antigen expression in medullary thymic epithelial cells. To maximize the diversity of self-antigen expression, Fezf2 and Aire utilized completely distinct transcriptional mechanisms, both of which were under the control of Chd4. Chd4 organized the promoter regions of Fezf2-dependent genes, while contributing to the Aire-mediated induction of self-antigens via super-enhancers. Mice deficient in Chd4 specifically in thymic epithelial cells exhibited autoimmune phenotypes, including T cell infiltration. Thus, Chd4 plays a critical role in integrating Fezf2- and Aire-mediated gene induction to establish central immune tolerance.

DOI: 10.1038/s41590-020-0717-2

Source: https://www.nature.com/articles/s41590-020-0717-2

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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