Thangamani Shankar, Kim Myughoo, Son Youngmin, Huang Xinxin, Kim Heejoo, Lee Jee H, Cho Jungyoon, Ulrich Benjamin, Broxmeyer Hal E, Kim Chang H
Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907;
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202;
J Immunol. 2015 Feb 1;194(3):883-6. doi: 10.4049/jimmunol.1401923. Epub 2014 Dec 29.
The two nuclear hormone receptor ligands progesterone and vitamin D (vit.D) play important roles in regulating T cells. The mechanism that connects these two hormones in regulating T cells has not been established. In this study, we report that progesterone is a novel inducer of vit.D receptor (VDR) in T cells and makes T cells highly sensitive to calcitriol. At the molecular level, the induction by progesterone is mediated by two progesterone receptor-binding elements in the intron region after the first noncoding exon of the human VDR gene. Increased expression of VDR by progesterone allows highly sensitive regulation of T cells by vit.D even when vit.D levels are suboptimal. This novel regulatory pathway allows enhanced induction of regulatory T cells but suppression of Th1 and Th17 cells by the two nuclear hormones. The results have significant ramifications in effective regulation of T cells to prevent adverse immune responses during pregnancy.
两种核激素受体配体孕酮和维生素D（vit.D）在调节T细胞中发挥重要作用。连接这两种激素调节T细胞的机制尚未明确。在本研究中，我们报告孕酮是T细胞中维生素D受体（VDR）的新型诱导剂，可使T细胞对骨化三醇高度敏感。在分子水平上，孕酮的诱导作用由人VDR基因第一个非编码外显子后的内含子区域中的两个孕酮受体结合元件介导。孕酮使VDR表达增加，即使在vit.D水平次优时，也能使vit.D对T细胞进行高度敏感的调节。这种新的调节途径使得两种核激素增强了对调节性T细胞的诱导，但抑制了Th1和Th17细胞。这些结果对于有效调节T细胞以预防孕期不良免疫反应具有重要意义。
