NFAT1 and JunB Cooperatively Regulate IL-31 Gene Expression in CD4+ T Cells in Health and Disease
SCIE
SCOPUS
- Title
- NFAT1 and JunB Cooperatively Regulate IL-31 Gene Expression in CD4+ T Cells in Health and Disease
- Authors
- Ji Sun Hwang; Gi-Cheon Kim; EunBee Park; Jung-Eun Kim; Chang-Suk Chae; Won Hwang; Changhon Lee; Sung-Min Hwang; Hui Sun Wang; Chang-Duk Jun; Dipayan Rudra; Im, SH
- Date Issued
- 2015-02-15
- Publisher
- American Association of Immunologists
- 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.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/27210
- DOI
- 10.4049/JIMMUNOL.1401862
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- Journal of Immunology, vol. 194, no. 4, page. 1963 - 1974, 2015-02-15
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