| First Author | Hwang JS | Year | 2015 |
| Journal | J Immunol | Volume | 194 |
| Issue | 4 | Pages | 1963-74 |
| PubMed ID | 25595785 | Mgi Jnum | J:345370 |
| Mgi Id | MGI:6839137 | Doi | 10.4049/jimmunol.1401862 |
| Citation | Hwang JS, et al. (2015) NFAT1 and JunB cooperatively regulate IL-31 gene expression in CD4+ T cells in health and disease. J Immunol 194(4):1963-74 |
| abstractText | 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. |
