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Bach2–Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop
- 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.
- Subjects :
- 0301 basic medicine
Male
Transcription, Genetic
Cellular differentiation
Science
General Physics and Astronomy
Biology
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Mice
Immune system
Th2 Cells
Transcription (biology)
BATF
Animals
Gene
Interleukin 4
Regulation of gene expression
Genetics
Mice, Knockout
Multidisciplinary
Cell Differentiation
General Chemistry
Cell biology
Mice, Inbred C57BL
Repressor Proteins
030104 developmental biology
Basic-Leucine Zipper Transcription Factors
Gene Expression Regulation
Regulatory sequence
Interferon Regulatory Factors
Female
Interleukin-4
STAT6 Transcription Factor
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....c7c8916b41fa0c8dcc2341388fb5eecb