Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the Promoter.

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 naïve human CD4 T cells. We show that in addition to the transcription factors AhR and RORγt, the active form of vitamin D (1,25(OH)D) 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)D-induced inhibition of 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 promoter and demonstrate that 1,25(OH)D-VDR directly inhibits IL-22 production this repressive VDRE.