Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 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 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.

Automated summary

Th22 cells are a CD4(+) T cell subset that produces interleukin (IL)-22 and primarily acts on epithelial cells, affecting keratinocyte proliferation, differentiation, and maturation. The regulation of IL-22 production in human T cells involves the transcription factors AhR and ROR gamma t, as well as the active form of vitamin D-3. The inhibition of IL-22 production by 1,25(OH)(2)D-3 through VDR and VDRE has been identified as a key mechanism.