1,25-Dihydroxyvitamin D3 selectively and reversibly impairs T helper-cell CNS localization

Inna V. Grishkan, Amanda N. Fairchild, Peter Calabresi, Anne R. Gocke

Research output: Contribution to journalArticle

Abstract

Pharmacologic targeting of T helper (TH) cell trafficking poses an attractive opportunity for amelioration of autoimmune diseases such as multiple sclerosis (MS). MS risk is associated with vitamin D deficiency, and its bioactive form, 1,25-dihydroxyvitamin D3 [1,25(OH)2D 3], has been shown to prevent experimental autoimmune encephalomyelitis, a mouse model of MS, via an incompletely understood mechanism. Herein, we systematically examined 1,25 (OH)2D3 effects on TH cells during their migration from the lymph nodes to the CNS. Our data demonstrate that myelin-reactive TH cells are successfully generated in the presence of 1,25(OH)2D3, secrete proinflammatory cytokines, and do not preferentially differentiate into suppressor T cells. These cells are able to leave the lymph node, enter the peripheral circulation, and migrate to the s. c. immunization sites. However, TH cells from 1,25(OH)2D3-treated mice are unable to enter the CNS parenchyma but are instead maintained in the periphery. Upon treatment cessation, mice rapidly develop experimental autoimmune encephalomyelitis, demonstrating that 1,25(OH)2D3 prevents the disease only temporarily likely by halting TH cell migration into the CNS.

Original languageEnglish (US)
Pages (from-to)21101-21106
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number52
DOIs
StatePublished - Dec 24 2013

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Calcitriol
Helper-Inducer T-Lymphocytes
Multiple Sclerosis
Autoimmune Experimental Encephalomyelitis
Lymph Nodes
Th1 Cells
Withholding Treatment
Vitamin D Deficiency
Myelin Sheath
Autoimmune Diseases
Cell Movement
Immunization
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • General

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1,25-Dihydroxyvitamin D3 selectively and reversibly impairs T helper-cell CNS localization. / Grishkan, Inna V.; Fairchild, Amanda N.; Calabresi, Peter; Gocke, Anne R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 52, 24.12.2013, p. 21101-21106.

Research output: Contribution to journalArticle

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