小柯机器人

近日，日本大阪大学Tomohiro Kurosaki、Yoshihiro Baba等研究人员合作发现，在B细胞中Tet2和Tet3通过抑制CD86来阻止自身免疫。2020年6月22日，该研究成果在线发表于《自然—免疫学》。

研究人员发现，B细胞中Tet（ten–eleven translocation）DNA去甲基化酶家族成员Tet2和Tet3的缺乏导致小鼠B和T细胞过度活化、自身抗体产生以及狼疮样疾病。从机制上讲，在没有Tet2和Tet3的情况下，通常不会发生CD86的下调，因为这是在自反应性B细胞长期暴露于自身抗原后发生的。Tet2和Tet3缺陷B细胞中CD86的表达失调可通过抗CD86阻断来限制T和B细胞异常激活（尽管并不完全）。缺乏Tet2和Tet3的B细胞在Cd86基因座处组蛋白去乙酰化酶1（HDAC1）和HDAC2的积累减少。

因此，这些发现表明，Tet2和Tet3介导的染色质修饰参与了自我反应性B细胞对CD86的抑制，这至少部分有助于预防自身免疫。

据悉，表观遗传修饰被认为对B细胞耐受具有贡献，但是没有直接证据。

附：英文原文

Title: Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity

Author: Shinya Tanaka, Wataru Ise, Takeshi Inoue, Ayako Ito, Chisato Ono, Yoshihito Shima, Shuhei Sakakibara, Manabu Nakayama, Kentaro Fujii, Ikuo Miura, Jafar Sharif, Haruhiko Koseki, Pandelakis A. Koni, Indu Raman, Quan-Zhen Li, Masato Kubo, Katsunori Fujiki, Ryuichiro Nakato, Katsuhiko Shirahige, Hiromitsu Araki, Fumihito Miura, Takashi Ito, Eiryo Kawakami, Yoshihiro Baba, Tomohiro Kurosaki

Issue&Volume: 2020-06-22

Abstract: A contribution of epigenetic modifications to B cell tolerance has been proposed but not directly tested. Here we report that deficiency of ten–eleven translocation (Tet) DNA demethylase family members Tet2 and Tet3 in B cells led to hyperactivation of B and T cells, autoantibody production and lupus-like disease in mice. Mechanistically, in the absence of Tet2 and Tet3, downregulation of CD86, which normally occurs following chronic exposure of self-reactive B cells to self-antigen, did not take place. The importance of dysregulated CD86 expression in Tet2- and Tet3-deficient B cells was further demonstrated by the restriction, albeit not complete, on aberrant T and B cell activation following anti-CD86 blockade. Tet2- and Tet3-deficient B cells had decreased accumulation of histone deacetylase 1 (HDAC1) and HDAC2 at the Cd86 locus. Thus, our findings suggest that Tet2- and Tet3-mediated chromatin modification participates in repression of CD86 on chronically stimulated self-reactive B cells, which contributes, at least in part, to preventing autoimmunity.

DOI: 10.1038/s41590-020-0700-y

Source: https://www.nature.com/articles/s41590-020-0700-y

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：31.25
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