title: Epigenetic reduction in invariant NKT cells following in utero vitamin D deficiency in mice.
abstract: Vitamin D status changes with season, but the effect of these changes on immune function is not clear. In this study, we show that in utero vitamin D deficiency in mice results in a significant reduction in invariant NKT (iNKT) cell numbers that could not be corrected by later intervention with vitamin D or 1,25-dihydroxy vitamin D(3) (active form of the vitamin). Furthermore, this was intrinsic to hematopoietic cells, as vitamin D-deficient bone marrow is specifically defective in generating iNKT cells in wild-type recipients. This vitamin D deficiency-induced reduction in iNKT cells is due to increased apoptosis of early iNKT cell precursors in the thymus. Whereas both the vitamin D receptor and vitamin D regulate iNKT cells, the vitamin D receptor is required for both iNKT cell function and number, and vitamin D (the ligand) only controls the number of iNKT cells. Given the importance of proper iNKT cell function in health and disease, this prenatal requirement for vitamin D suggests that in humans, the amount of vitamin D available in the environment during prenatal development may dictate the number of iNKT cells and potential risk of autoimmunity.
authors.affiliation: Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802. USA.
authors.forename: Sanhong
authors.initials: S
authors.lastname: Yu
authors.forename: Margherita T
authors.initials: MT
authors.lastname: Cantorna
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000172:deficiency / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D044127:Epigenesis, Genetic / Q000276:immunology*; D005260:Female; D005679:G(M3) Ganglioside / Q000008:administration & dosage; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D014807:Vitamin D / Q000008:administration & dosage; D014808:Vitamin D Deficiency / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
chemical_list: D005679:G(M3) Ganglioside; D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase