Abstract
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.
Highlights
Various subsets of effector CD4+ T helper (Th) cells, classified by the lineage-specific master transcription factors they express and the cytokines they secrete, have been described [1, 2]
One study has identified IL-1b and IL-23 as the optimal cytokine cocktail to generate Th22 cells that do not produce IL-17 [20], whereas another study found that tumour necrosis factor (TNF) and IL-6 were required for optimal Th22 cell generation [4]
We show that 1,25(OH)2D3 inhibits IL-22 expression and production in human Th22 cells through a repressive vitamin D response element (VDRE) in the il22 promoter. 1,25(OH)2D3 is well-known by its immunomodulatory properties and it can influence the differentiation of T helper cells by regulating the production of their signature cytokine [35,36,37,38,39,40,41]
Summary
Various subsets of effector CD4+ T helper (Th) cells, classified by the lineage-specific master transcription factors they express and the cytokines they secrete, have been described [1, 2]. Th22 cells constitute a recently described CD4+ T cell subset defined by their production of interleukin (IL)-22 [3, 4]. The biological functions of IL-22 is mainly restricted to non-hematopoietic cells such as epithelial cells located in the skin, gut, lung, liver, pancreas and kidney [5,6,7]. The role of IL-22 in epithelial homeostasis is further underlined by its association to inflammatory skin and gut diseases such as atopic dermatitis [14, 15], psoriasis [16] and colorectal cancers [17].
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call