NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice

Amanda Waddell, Jun Zhao, Margherita Teresa-Anna Cantorna

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Active vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying 1,25D3's anti-inflammatory properties are not fully understood. We employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of NKT cells in 1,25D3-mediated protection from EAE. Wild-type (WT) mice or mice lacking all NKT cells (CD1d-/-) or invariant NKT cells (Jα18-/-) were fed control or 1,25D3-supplemented diets. All mice fed with the control diet developed severe EAE. 1,25D3 treatment of WT mice protected them from developing EAE. CD1d-/- and Jα18-/- mice treated with 1,25D3 were not protected to the same extent as WT mice. Myelin oligodendrocyte glycoprotein-specific IL-17 and IFN-γ production was significantly reduced in 1,25D3 WT mice compared with WT but was not decreased in 1,25D3 CD1d-/- mice compared with CD1d-/- mice. IL-4-/- mice were utilized to determine how IL-4 deficiency affects susceptibility to EAE. IL-4-/- mice were not protected from developing EAE by α-galactosylceramide (α-GalCer) or 1,25D3 treatment. Furthermore, 1,25D3 treatment of splenocytes in vitro decreased α-GalCer-induced IL-17 and increased IL-4, IL-5 and IL-10 production. 1,25D3 alters the cytokine profile of invariant NKT cells in vitro. These studies demonstrate that NKT cells are important mediators of 1,25D3-induced protection from EAE in mice and NKT cell-derived IL-4 may be an important factor in providing this protection.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalInternational Immunology
Volume27
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

Natural Killer T-Cells
Autoimmune Experimental Encephalomyelitis
Calcitriol
Interleukin-4
Interleukin-17
Myelin-Oligodendrocyte Glycoprotein
Galactosylceramides
Diet
Interleukin-5
Vitamin D
Interleukin-10
Autoimmune Diseases
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

@article{1ac67739124e46d18922b65d97950439,
title = "NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice",
abstract = "Active vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying 1,25D3's anti-inflammatory properties are not fully understood. We employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of NKT cells in 1,25D3-mediated protection from EAE. Wild-type (WT) mice or mice lacking all NKT cells (CD1d-/-) or invariant NKT cells (Jα18-/-) were fed control or 1,25D3-supplemented diets. All mice fed with the control diet developed severe EAE. 1,25D3 treatment of WT mice protected them from developing EAE. CD1d-/- and Jα18-/- mice treated with 1,25D3 were not protected to the same extent as WT mice. Myelin oligodendrocyte glycoprotein-specific IL-17 and IFN-γ production was significantly reduced in 1,25D3 WT mice compared with WT but was not decreased in 1,25D3 CD1d-/- mice compared with CD1d-/- mice. IL-4-/- mice were utilized to determine how IL-4 deficiency affects susceptibility to EAE. IL-4-/- mice were not protected from developing EAE by α-galactosylceramide (α-GalCer) or 1,25D3 treatment. Furthermore, 1,25D3 treatment of splenocytes in vitro decreased α-GalCer-induced IL-17 and increased IL-4, IL-5 and IL-10 production. 1,25D3 alters the cytokine profile of invariant NKT cells in vitro. These studies demonstrate that NKT cells are important mediators of 1,25D3-induced protection from EAE in mice and NKT cell-derived IL-4 may be an important factor in providing this protection.",
author = "Amanda Waddell and Jun Zhao and Cantorna, {Margherita Teresa-Anna}",
year = "2015",
month = "5",
day = "1",
doi = "10.1093/intimm/dxu147",
language = "English (US)",
volume = "27",
pages = "237--244",
journal = "International Immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "5",

}

NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice. / Waddell, Amanda; Zhao, Jun; Cantorna, Margherita Teresa-Anna.

In: International Immunology, Vol. 27, No. 5, 01.05.2015, p. 237-244.

Research output: Contribution to journalArticle

TY - JOUR

T1 - NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice

AU - Waddell, Amanda

AU - Zhao, Jun

AU - Cantorna, Margherita Teresa-Anna

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Active vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying 1,25D3's anti-inflammatory properties are not fully understood. We employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of NKT cells in 1,25D3-mediated protection from EAE. Wild-type (WT) mice or mice lacking all NKT cells (CD1d-/-) or invariant NKT cells (Jα18-/-) were fed control or 1,25D3-supplemented diets. All mice fed with the control diet developed severe EAE. 1,25D3 treatment of WT mice protected them from developing EAE. CD1d-/- and Jα18-/- mice treated with 1,25D3 were not protected to the same extent as WT mice. Myelin oligodendrocyte glycoprotein-specific IL-17 and IFN-γ production was significantly reduced in 1,25D3 WT mice compared with WT but was not decreased in 1,25D3 CD1d-/- mice compared with CD1d-/- mice. IL-4-/- mice were utilized to determine how IL-4 deficiency affects susceptibility to EAE. IL-4-/- mice were not protected from developing EAE by α-galactosylceramide (α-GalCer) or 1,25D3 treatment. Furthermore, 1,25D3 treatment of splenocytes in vitro decreased α-GalCer-induced IL-17 and increased IL-4, IL-5 and IL-10 production. 1,25D3 alters the cytokine profile of invariant NKT cells in vitro. These studies demonstrate that NKT cells are important mediators of 1,25D3-induced protection from EAE in mice and NKT cell-derived IL-4 may be an important factor in providing this protection.

AB - Active vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying 1,25D3's anti-inflammatory properties are not fully understood. We employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of NKT cells in 1,25D3-mediated protection from EAE. Wild-type (WT) mice or mice lacking all NKT cells (CD1d-/-) or invariant NKT cells (Jα18-/-) were fed control or 1,25D3-supplemented diets. All mice fed with the control diet developed severe EAE. 1,25D3 treatment of WT mice protected them from developing EAE. CD1d-/- and Jα18-/- mice treated with 1,25D3 were not protected to the same extent as WT mice. Myelin oligodendrocyte glycoprotein-specific IL-17 and IFN-γ production was significantly reduced in 1,25D3 WT mice compared with WT but was not decreased in 1,25D3 CD1d-/- mice compared with CD1d-/- mice. IL-4-/- mice were utilized to determine how IL-4 deficiency affects susceptibility to EAE. IL-4-/- mice were not protected from developing EAE by α-galactosylceramide (α-GalCer) or 1,25D3 treatment. Furthermore, 1,25D3 treatment of splenocytes in vitro decreased α-GalCer-induced IL-17 and increased IL-4, IL-5 and IL-10 production. 1,25D3 alters the cytokine profile of invariant NKT cells in vitro. These studies demonstrate that NKT cells are important mediators of 1,25D3-induced protection from EAE in mice and NKT cell-derived IL-4 may be an important factor in providing this protection.

UR - http://www.scopus.com/inward/record.url?scp=84929365666&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929365666&partnerID=8YFLogxK

U2 - 10.1093/intimm/dxu147

DO - 10.1093/intimm/dxu147

M3 - Article

C2 - 25574039

AN - SCOPUS:84929365666

VL - 27

SP - 237

EP - 244

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 5

ER -