Vitamin D Inhibits Il-22 Production Through A Repressive Vitamin D Response Element In The Il22 Promoter

FRONTIERS IN IMMUNOLOGY(2021)

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摘要
Th22 cells constitute a recently described CD4(+) T cell subset defined by its production of interleukin (IL)-22. The action of IL-22 is mainly restricted to epithelial cells. IL-22 enhances keratinocyte proliferation but inhibits their differentiation and maturation. Dysregulated IL-22 production has been associated to some inflammatory skin diseases such as atopic dermatitis and psoriasis. How IL-22 production is regulated in human T cells is not fully known. In the present study, we identified conditions to generate Th22 cells that do not co-produce IL-17 from naive human CD4(+) T cells. We show that in addition to the transcription factors AhR and ROR gamma t, the active form of vitamin D-3 (1,25(OH)(2)D-3) regulates IL-22 production in these cells. By studying T cells with a mutated vitamin D receptor (VDR), we demonstrate that the 1,25(OH)(2)D-3-induced inhibition of il22 gene transcription is dependent on the transcriptional activity of the VDR in the T cells. Finally, we identified a vitamin D response element (VDRE) in the il22 promoter and demonstrate that 1,25(OH)(2)D-3-VDR directly inhibits IL-22 production via this repressive VDRE.
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关键词
Th22 cells, IL-22, IL-17, vitamin D, vitamin D receptor, vitamin D response element (VDRE)
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