RRC ID 47675
Author Kuwahara M, Ise W, Ochi M, Suzuki J, Kometani K, Maruyama S, Izumoto M, Matsumoto A, Takemori N, Takemori A, Shinoda K, Nakayama T, Ohara O, Yasukawa M, Sawasaki T, Kurosaki T, Yamashita M.
Title Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop.
Journal Nat Commun
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.
Volume 7
Pages 12596
Published 2016-9-1
DOI 10.1038/ncomms12596
PII ncomms12596
PMID 27581382
PMC PMC5025763
MeSH Animals Basic-Leucine Zipper Transcription Factors / genetics* Basic-Leucine Zipper Transcription Factors / metabolism* Cell Differentiation / immunology Female Gene Expression Regulation Interferon Regulatory Factors / genetics* Interferon Regulatory Factors / metabolism Interleukin-4 / biosynthesis Interleukin-4 / immunology Male Mice Mice, Inbred C57BL Mice, Knockout Repressor Proteins / genetics* Repressor Proteins / metabolism STAT6 Transcription Factor / genetics Th2 Cells / immunology* Transcription, Genetic / genetics
IF 11.878
Times Cited 31
WOS Category IMMUNOLOGY
Resource
DNA material pCMV-HA-Bach2 wt (RDB14569) pCMV-HA-Bach2 L687A (RDB14570) pCMV-HA-Bach2 L694A (RDB14571) pCMV-Myc-Batf (RDB14572).