Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop.
Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop.
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DOI：
10.1038/ncomms12596
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发表时间：
2016-09-01
影响因子：
16.6
通讯作者：
Yamashita, Masakatsu
中科院分区：
文献类型：
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作者：
Kuwahara, Makoto;Ise, Wataru;Ochi, Mizuki;Suzuki, Junpei;Kometani, Kohei;Maruyama, Saho;Izumoto, Maya;Matsumoto, Akira;Takemori, Nobuaki;Takemori, Ayako;Shinoda, Kenta;Nakayama, Toshinori;Ohara, Osamu;Yasukawa, Masaki;Sawasaki, Tatsuya;Kurosaki, Tomohiro;Yamashita, Masakatsu
虽然Bach 2在调节Th 2型免疫应答中具有重要作用，但其潜在的分子机制仍不清楚。我们在此证明Bach 2与Batf相关，并结合到Th 2细胞因子基因座的调控区。Bach 2-Batf复合物拮抗Batf-Irf 4复合物向AP-1基序的募集并抑制Th 2细胞因子产生。此外，我们发现Bach 2通过两种不同的途径调节Batf和Batf 3的表达。首先，Bach 2通过抑制IL-4的产生来抑制Batf和Batf 3表达的维持。第二，Bach 2-Batf复合物直接结合Batf和Batf 3基因座，并通过干扰Batf-Irf 4复合物来降低转录。这些发现表明，IL-4和Batf形成正反馈放大环，以诱导Th 2细胞分化和随后的Th 2型免疫应答，并且需要Bach 2-Batf相互作用来防止过度的Th 2应答。 Bach 2限制T细胞效应子功能。在这里，作者表明Bach 2-Batf复合物拮抗Batf-Irf 4复合物向AP-1基序的募集并抑制Th 2细胞因子的产生，并描述了Bach 2限制Baft介导的Th 2应答的负反馈机制。
Although Bach2 has an important role in regulating the Th2-type immune response, the underlying molecular mechanisms remain unclear. We herein demonstrate that Bach2 associates with Batf and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2–Batf complex antagonizes the recruitment of the Batf–Irf4 complex to AP-1 motifs and suppresses Th2 cytokine production. Furthermore, we find that Bach2 regulates the Batf and Batf3 expressions via two distinct pathways. First, Bach2 suppresses the maintenance of the Batf and Batf3 expression through the inhibition of IL-4 production. Second, the Bach2–Batf complex directly binds to the Batf and Batf3 gene loci and reduces transcription by interfering with the Batf–Irf4 complex. These findings suggest that IL-4 and Batf form a positive feedback amplification loop to induce Th2 cell differentiation and the subsequent Th2-type immune response, and Bach2–Batf interactions are required to prevent an excessive Th2 response. Bach2 limits T cell effector functions. Here the authors show that Bach2–Batf complex antagonizes the recruitment of the Batf–Irf4 complex to AP-1 motifs and suppresses Th2 cytokine production, and describe mechanisms of negative feedback by which Bach2 restricts Baft-mediated Th2 response.
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影响因子：
16.6
作者：
Kuwahara, Makoto;Suzuki, Junpei;Tofukuji, Soichi;Yamada, Takeshi;Kanoh, Makoto;Matsumoto, Akira;Maruyama, Saho;Kometani, Kohei;Kurosaki, Tomohiro;Ohara, Osamu;Nakayama, Toshinori;Yamashita, Masakatsu
通讯作者：
Yamashita, Masakatsu
影响因子：
64.8
作者：
通讯作者：
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影响因子：
4.4
作者：
Matsuoka, Kazuhiro;Komori, Hiroaki;Nose, Masato;Endo, Yaeta;Sawasaki, Tatsuya
通讯作者：
Sawasaki, Tatsuya
影响因子：
8
作者：
Echlin, DR;Tae, HJ;Taparowsky, EJ
通讯作者：
Taparowsky, EJ
DOI：
10.4049/jimmunol.1302378
发表时间：
2014-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kim EH;Gasper DJ;Lee SH;Plisch EH;Svaren J;Suresh M
通讯作者：
Suresh M