Regulation of IL-10, IL-21 and IL-22 gene expression by the Basic Region of c-Maf in Th17 cells
Date Issued
2012
Date
2012
Author(s)
Lu, Yu-Jung
Abstract
In addition to act as IL-4 activator in Th2 cells, c-Maf has been demonstrated to activate IL-10 and IL-21 directly in Th17 cells. Recently, c-Maf has also been discovered to be the downstream of TGF-β,and inhibit IL-22 production. As a transcription factor, the basic region of c-Maf plays a significant role in recognizing the MARE site, Maf recognition element. Several mutations in the basic region of c-Maf have been reported to cause congenital cataracts in human. Since the basic region of c-Maf play an important role in the DNA-binding, we plan to investigate whether the mutants in c-Maf basic region, including K294R, R296S and Y298F, affect their transactivation abilities on cytokine gene expression.
Retroviral transduction was performed to express the WT or mutant c- Mafs in the IL-6-skewing CD4+ T cells, and the cytokine expression was assayed by ELISA and real-time PCR. We observed that the IL-10 and IL-21 production were impaired in c-Maf BR mutants. In further investigation of the mechanism involved, we discovered that the cellular distribution of all mutants was changed. In addition, all mutant proteins were less stable than WT c-Maf. These phenomena may contribute partially to the reduction of cytokine production of c-Maf BR mutants.
Subjects
c-Maf
IL-10
IL-21
IL-22
Th17 cells
Type
thesis
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