1,25-Dihydroxyvitamin D3 acts directly on the T lymphocyte vitamin D receptor to inhibit experimental autoimmune encephalomyelitis. Eur J Immunol 2011 Mar;41(3):822-32
Date
02/03/2011Pubmed ID
21287548DOI
10.1002/eji.201040632Scopus ID
2-s2.0-79951782445 (requires institutional sign-in at Scopus site) 140 CitationsAbstract
Multiple sclerosis (MS) is an incurable autoimmune neurodegenerative disease. Environmental factors may be key to MS prevention and treatment. MS prevalence and severity decrease with increasing sunlight exposure and vitamin D(3) supplies, supporting our hypothesis that the sunlight-dependent hormone, 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2) D(3) ), inhibits autoimmune T-cell responses in MS. Moreover, 1,25-(OH)(2) D(3) inhibits and reverses experimental autoimmune encephalomyelitis (EAE), an MS model. Here, we investigated whether 1,25-(OH)(2) D(3) inhibits EAE via the vitamin D receptor (VDR) in T lymphocytes. Using bone marrow chimeric mice with a disrupted VDR only in radio-sensitive hematopoietic cells or radio-resistant non-hematopoietic cells, we found that hematopoietic cell VDR function was necessary for 1,25-(OH)(2) D(3) to inhibit EAE. Furthermore, conditional targeting experiments showed that VDR function in T cells was necessary. Neither 1,25-(OH)(2) D(3) nor T-cell-specific VDR targeting influenced CD4(+) Foxp3(+) T-cell proportions in the periphery or the CNS in these studies. These data support a model wherein 1,25-(OH)(2) D(3) acts directly on pathogenic CD4(+) T cells to inhibit EAE.
Author List
Mayne CG, Spanier JA, Relland LM, Williams CB, Hayes CEAuthor
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcitriol
Encephalomyelitis, Autoimmune, Experimental
Female
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Receptors, Calcitriol
T-Lymphocyte Subsets
T-Lymphocytes
