AUTHOR=Lopez Daniel V. , Al-Jaberi Fatima A.H. , Damas Nkerorema D. , Weinert Brian T. , Pus Urska , Torres-Rusillo Sara , Woetmann Anders , Ødum Niels , Bonefeld Charlotte M. , Kongsbak-Wismann Martin , Geisler Carsten 

TITLE=Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.715059

DOI=10.3389/fimmu.2021.715059

ISSN=1664-3224

ABSTRACT=<p>Th22 cells constitute a recently described CD4<sup>+</sup> 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<sup>+</sup> T cells. We show that in addition to the transcription factors AhR and RORγt, the active form of vitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) 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)<sub>2</sub>D<sub>3</sub>-induced inhibition of <italic>il22</italic> 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 <italic>il22</italic> promoter and demonstrate that 1,25(OH)<sub>2</sub>D<sub>3</sub>-VDR directly inhibits IL-22 production <italic>via</italic> this repressive VDRE.</p>