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Ultraviolet irradiation promotes FOXP3 transcription via p53 in psoriasis
Author(s) -
Zhang Dongmei,
Chen Yang,
Chen Ling,
Yang Riyao,
Wang Li,
Liu Wenying,
Zhai Zhifang,
Shen Zhu
Publication year - 2016
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12942
Subject(s) - foxp3 , chromatin immunoprecipitation , chemistry , transcription factor , psoriasis , cancer research , microbiology and biotechnology , microphthalmia associated transcription factor , downregulation and upregulation , biology , immune system , immunology , promoter , gene expression , gene , biochemistry
The decrease of forkhead box P3‐positive ( FOXP 3 + ) regulatory T cells (Tregs) causes an immune imbalance with effector T cells in psoriasis. Previous studies have demonstrated that in addition to its known effects on keratinocytes and effector T cells, ultraviolet ( UV ) irradiation alleviates psoriasis via the upregulation of FOXP 3 + Tregs. However, the mechanism is unclear. Here, we found that FOXP 3 + T cells were increased in psoriatic lesions after UVB irradiation ( t ' = 3.7006, P < 0.01), as determined by immunohistochemical staining. In addition, the levels of FOXP 3 and p53, one of the downstream targets of UV irradiation, showed accordant changes after UV irradiation. Experiments that used a MAPK inhibitor, p53 mutant cell lines, p53 inhibitor and p53 sh RNA showed a decrease in FOXP 3 levels, suggesting that p53 is required for UV ‐induced FOXP 3 transcription. Next, we demonstrated that there are two binding sites for p53 on FOXP 3 by informatics tools, a dual‐luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. One binding site (−1771 to −1583) is located at the promoter region and is adjacent to a previously reported p53‐binding region in breast cancer cells. The other (+3845 to +4042) is located within the first intron and has not been previously reported. Our study demonstrated that FOXP 3 is regulated, at least in part, by the binding of p53 to several binding sites in the promoter and intron regions following UV irradiation in psoriasis. It will be helpful to further clarify the regulatory mechanism of FOXP 3 transcription and to provide new insights into the mechanisms that mediate the effects of UV irradiation in autoimmune skin disorders.