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

• Vitamin D supplementation alone does not reverse demyelinating disease in rodents.
• One calcitriol dose induced demyelinating disease remissions, but all animals relapsed.
• One calcitriol dose plus vitamin D sustainably reversed demyelinating disease.
• Calcitriol and vitamin D transiently induced Helios and FoxP3-expressing T cells.
• Calcitriol and vitamin D sustainably depleted T cells from the central nervous system.

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.