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Vitamin D3-mediated resistance to a multiple sclerosis model disease depends on myeloid cell 1,25-dihydroxyvitamin D3 synthesis and correlates with increased CD4+ T cell CTLA-4 expression.
Spanier, Justin A; Nashold, Faye E; Nelson, Corwin D; Praska, Corinne E; Hayes, Colleen E.
Afiliación
  • Spanier JA; Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, MN, USA. Electronic address: span0005@umn.edu.
  • Nashold FE; Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI, USA.
  • Nelson CD; Department of Animal Sciences, University of Florida, Gainesville, FL, USA.
  • Praska CE; Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI, USA.
  • Hayes CE; Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI, USA.
J Neuroimmunol ; 338: 577105, 2020 01 15.
Article en En | MEDLINE | ID: mdl-31731231
Microglial cell activation is the earliest biomarker of the inflammatory processes that cause central nervous system (CNS) lesions in multiple sclerosis. We hypothesized that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) production by activated microglia and macrophages in the CNS inhibits these inflammatory processes. To test this hypothesis, we targeted the Cyp27b1 gene specifically in myeloid cells, then analyzed the influence of disrupted myeloid cell 1,25-(OH)2D3 synthesis on vitamin D3-mediated resistance to experimental autoimmune encephalomyelitis (EAE). Myeloid cell 1,25-(OH)2D3 synthesis was essential for vitamin D3-mediated EAE resistance. Increased CTLA-4 expression in the CNS-infiltrating CD4+ Tconv and Treg cells and decreased splenic B cell CD86 expression correlated with resistance. These new data provide solid support for the view that vitamin D3 reduces MS risk in part through a mechanism involving myeloid cell 1,25-(OH)2D3 production and CTLA-4 upregulation in CNS-infiltrating CD4+ T cells. We suggest that CTLA-4 serves as a vitamin D3-regulated immunological checkpoint in multiple sclerosis prevention.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcitriol / Linfocitos T CD4-Positivos / Microglía / Colecalciferol / Encefalomielitis Autoinmune Experimental / Antígeno CTLA-4 / Macrófagos Límite: Animals Idioma: En Revista: J Neuroimmunol Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcitriol / Linfocitos T CD4-Positivos / Microglía / Colecalciferol / Encefalomielitis Autoinmune Experimental / Antígeno CTLA-4 / Macrófagos Límite: Animals Idioma: En Revista: J Neuroimmunol Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos