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Bach2–Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop

Authors :
Toshinori Nakayama
Osamu Ohara
Tatsuya Sawasaki
Junpei Suzuki
Akira Matsumoto
Ayako Takemori
Nobuaki Takemori
Kohei Kometani
Maya Izumoto
Makoto Kuwahara
Masaki Yasukawa
Saho Maruyama
Masakatsu Yamashita
Kenta Shinoda
Tomohiro Kurosaki
Wataru Ise
Mizuki Ochi
Source :
Nature Communications, Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016)
Publication Year :
2016
Publisher :
Nature Publishing Group, 2016.

Abstract

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.<br />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.

Details

Language :
English
ISSN :
20411723
Volume :
7
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.doi.dedup.....c7c8916b41fa0c8dcc2341388fb5eecb