The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
Front Immunol. 2021 Aug 2;12:715059. doi: 10.3389/fimmu.2021.715059. eCollection 2021.
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.
Th22 细胞是新近被描述的 CD4 T 细胞亚群，其特征是能够产生白细胞介素（IL）-22。IL-22 的作用主要局限于上皮细胞。IL-22 可增强角质形成细胞的增殖，但抑制其分化和成熟。IL-22 的失调产生与一些炎症性皮肤疾病有关，如特应性皮炎和银屑病。在人类 T 细胞中，IL-22 的产生是如何被调控的目前还不完全清楚。在本研究中，我们确定了从初始人类 CD4 T 细胞中生成不共同产生 IL-17 的 Th22 细胞的条件。我们发现，除了转录因子 AhR 和 RORγt 之外，活性形式的维生素 D（1,25(OH)D）也可调节这些细胞中 IL-22 的产生。通过研究具有突变维生素 D 受体（VDR）的 T 细胞，我们证明 1,25(OH)D 诱导的基因转录抑制依赖于 T 细胞中 VDR 的转录活性。最后，我们在 基因启动子中鉴定出一个维生素 D 反应元件（VDRE），并证明 1,25(OH)D-VDR 可直接通过该抑制性 VDRE 抑制 IL-22 的产生。
