One calcitriol dose transiently increases Helios+ FoxP3+ T cells and ameliorates autoimmune demyelinating disease

J Neuroimmunol. 2013 Oct 15;263(1-2):64-74. doi: 10.1016/j.jneuroim.2013.07.016. Epub 2013 Aug 6.

Abstract

Multiple sclerosis (MS) is an incurable inflammatory demyelinating disease. We investigated one calcitriol dose plus vitamin D3 (calcitriol/+D) as a demyelinating disease treatment in experimental autoimmune encephalomyelitis (EAE). Evidence that calcitriol-vitamin D receptor pathway deficits may promote MS, and data showing calcitriol enhancement of autoimmune T cell apoptosis provided the rationale. Whereas vitamin D3 alone was ineffective, calcitriol/+D transiently increased central nervous system (CNS) Helios(+)FoxP3(+) T cells and sustainably decreased CNS T cells, pathology, and neurological deficits in mice with EAE. Calcitriol/+D, which was more effective than methylprednisolone, has potential for reversing inflammatory demyelinating disease safely and cost-effectively.

Keywords: Autoimmunity; Encephalomyelitis; Methylprednisolone; Multiple sclerosis; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitriol / administration & dosage*
  • Cattle
  • DNA-Binding Proteins / biosynthesis*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Forkhead Transcription Factors / biosynthesis*
  • Lymphocyte Count
  • Male
  • Mice
  • Random Allocation
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Transcription Factors / biosynthesis*
  • Up-Regulation / drug effects
  • Up-Regulation / immunology*

Substances

  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Transcription Factors
  • Zfpn1a2 protein, mouse
  • Calcitriol