title: Cutting edge: progesterone directly upregulates vitamin d receptor gene expression for efficient regulation of T cells by calcitriol.
abstract: 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.
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907;
authors.forename: Shankar
authors.initials: S
authors.lastname: Thangamani
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907;
authors.forename: Myughoo
authors.initials: M
authors.lastname: Kim
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907;
authors.forename: Youngmin
authors.initials: Y
authors.lastname: Son
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202;
authors.forename: Xinxin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907;
authors.forename: Heejoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907;
authors.forename: Jee H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907;
authors.forename: Jungyoon
authors.initials: J
authors.lastname: Cho
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ulrich
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202;
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.affiliation: 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; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907; and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907 chkim@purdue.edu.
authors.forename: Chang H
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D030181:Vitamin D Response Element
chemical_list: D018167:Receptors, Calcitriol; D011374:Progesterone; D002117:Calcitriol