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

First Author  Kuwahara M Year  2016
Journal  Nat Commun Volume  7
Pages  12596 PubMed ID  27581382
Mgi Jnum  J:241902 Mgi Id  MGI:5903834
Doi  10.1038/ncomms12596 Citation  Kuwahara M, et al. (2016) Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop. Nat Commun 7:12596
abstractText  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.
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