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NFAT1 and JunB Cooperatively Regulate IL-31 Gene Expression in CD4+ T Cells in Health and Disease
- Source :
- The Journal of Immunology. 194:1963-1974
- Publication Year :
- 2015
- Publisher :
- The American Association of Immunologists, 2015.
-
Abstract
- IL-31 is a key mediator of itching in atopic dermatitis (AD) and is preferentially produced by activated CD4+ T cells and Th2 cells. Although pathophysiological functions of IL-31 have been suggested in diverse immune disorders, the molecular events underlying IL-31 gene regulation are still unclear. In this study we identified the transcription start site and functional promoter involved in IL-31 gene regulation in mouse CD4+ T cells. TCR stimulation–dependent IL-31 expression was found to be closely linked with in vivo binding of NFAT1 and JunB to the IL-31 promoter. Although NFAT1 alone enhanced IL-31 promoter activity, it was further enhanced in the presence of JunB. Conversely, knockdown of either NFAT1 or JunB resulted in reduced IL-31 expression. NFAT1-deficient CD4+ T cells showed a significant defect in IL-31 expression compared with wild-type CD4+ T cells. In agreement with these findings, mice subjected to atopic conditions showed much higher levels of IL-31, which were closely correlated with a significant increase in the number of infiltrated NFAT1+CD4+ T cells into the AD ears. Amelioration of AD progression by cyclosporin A treatment was well correlated with downregulation of IL-31 expressions in CD4+ T cells and total ear residual cells. In summary, our results suggest a functional cooperation between NFAT1 and JunB in mediating IL-31 gene expression in CD4+ T cells and indicate that interference with this interaction or their activity has the potential of reducing IL-31–mediated AD symptoms.
- Subjects :
- CD4-Positive T-Lymphocytes
Chromatin Immunoprecipitation
JUNB
Immunology
Biology
Real-Time Polymerase Chain Reaction
Transfection
Dermatitis, Atopic
Mice
Interleukin 21
Immune system
Cyclosporin a
Gene expression
Animals
Immunology and Allergy
RNA, Small Interfering
Regulation of gene expression
Mice, Inbred BALB C
Gene knockdown
NFATC Transcription Factors
Interleukins
T-cell receptor
Immunohistochemistry
Molecular biology
Mice, Inbred C57BL
Disease Models, Animal
Gene Expression Regulation
Mutagenesis, Site-Directed
Female
Transcriptome
Transcription Factors
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 194
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....3a7f30b5895b1f2f357e01db33ce18ca