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Transcriptional activation of the IL31 gene by NFAT and STAT6

 Keunhee Park  ;  Joo-Hong Park  ;  Wook-Jin Yang  ;  Jong-Joo Lee  ;  Min-Ji Song  ;  Hyoung-Pyo Kim 
 Journal of Leukocyte Biology, Vol.91(2) : 245-257, 2012 
Journal Title
 Journal of Leukocyte Biology 
Issue Date
IL-31, a newly identified member of the IL-6 cytokine family, is involved in many pathological conditions, including atopic dermatitis and pruritis. In this study, we investigated how expression of IL-31 is regulated in T cells and mast cells. We observed that expression of IL-31 required a calcium signal and was dependent on the calcineurin-NFAT signaling pathway. Moreover, we found that IL-31 promoter contains a positive regulatory region that mediates calcium- and IL-4-dependent induction of the IL-31 gene and demonstrated that a change into an open chromatin conformation occurs in this region after stimulation with calcium and IL-4. Whereas IL-4 responsiveness required STAT6 binding sites, calcium responsiveness of IL-31 promoter required NFAT binding sites that bind NFATc1 and NFATc2 in vitro and in vivo. The induction of IL-31 promoter activity was impaired when these sites were mutated but was enhanced by CA-NFATc1 or STAT6 proteins and further increased synergistically by combinations of both proteins. Furthermore, the importance of STAT6 proteins was indicated by impaired, IL-4-mediated induction of IL-31 in STAT6-diminished Jurkat cells. Thus, our data demonstrate that calcium and IL-4 signals are required to mediate induction of IL-31 in Th2 cells and mast cells and that this induction appears to result from specific binding of NFAT and STAT6 proteins.
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1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
김형표(Kim, Hyoung Pyo) ORCID logo https://orcid.org/0000-0003-1441-8822
박근희(Park, Keun Hee)
박주홍(Park, Joo Hong)
송민지(Song, Min Ji)
이종주(Lee, Jong Joo)
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