Journal article
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 naïve human CD4+ T cells. We show that in addition to the transcription factors AhR and RORγt, the active form of vitamin D3 (1,25(OH)2D3) 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)2D3-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)2D3-VDR directly inhibits IL-22 production via this repressive VDRE.
Language: | English |
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Publisher: | Frontiers Media S.A. |
Year: | 2021 |
Pages: | 715059 |
ISSN: | 16643224 |
Types: | Journal article |
DOI: | 10.3389/fimmu.2021.715059 |
ORCIDs: | 0000-0003-2271-7283 , 0000-0002-3016-1652 , 0000-0002-3008-735X , 0000-0003-3135-5624 , 0000-0002-0523-6229 , 0000-0002-3496-9333 and 0000-0002-8472-0771 |
AHR protein, human Basic Helix-Loop-Helix Transcription Factors Binding Sites Biomarkers Cell Line Cytokines Gene Expression Regulation Humans IL-17 IL-22 Immunologic diseases. Allergy Inflammation Mediators Interleukin-22 Interleukins Nuclear Receptor Subfamily 1, Group F, Member 3 Nucleotide Motifs Promoter Regions, Genetic Protein Binding RC581-607 Receptors, Aryl Hydrocarbon Receptors, Calcitriol T-Lymphocyte Subsets Th22 cells Vitamin D Vitamin D Response Element vitamin D vitamin D receptor vitamin D response element (VDRE)