1,25-Dihydroxyvitamin D 3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A

Sneha Joshi, Luiz Carlos Pantalena, Xikui K. Liu, Sarah L. Gaffen, Hong Liu, Christine Rohowsky-Kochan, Kenji Ichiyama, Akihiko Yoshimura, Lawrence Steinman, Sylvia Christakos, Sawsan Youssef

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

A new class of inflammatory CD4 + T cells that produce interleukin-17 (IL-17) (termed Th17) has been identified, which plays a critical role in numerous inflammatory conditions and autoimmune diseases. The active form of vitamin D, 1,25-dihydroxyvitamin D 3 [1,25(OH) 2D 3], has a direct repressive effect on the expression of IL-17A in both human and mouse T cells. In vivo treatment of mice with ongoing experimental autoimmune encephalomyelitis (EAE; a mouse model of multiple sclerosis) diminishes paralysis and progression of the disease and reduces IL-17A-secreting CD4 + T cells in the periphery and central nervous system (CNS). The mechanism of 1,25(OH) 2D 3 repression of IL-17A expression was found to be transcriptional repression, mediated by the vitamin D receptor (VDR). Transcription assays, gel shifting, and chromatin immunoprecipitation (ChIP) assays indicate that the negative effect of 1,25(OH) 2D 3 on IL-17A involves blocking of nuclear factor for activated T cells (NFAT), recruitment of histone deacetylase (HDAC), sequestration of Runt-related transcription factor 1 (Runx1) by 1,25(OH) 2D 3/VDR, and a direct effect of 1,25(OH) 2D 3 on induction of Foxp3. Our results describe novel mechanisms and new concepts with regard to vitamin D and the immune system and suggest therapeutic targets for the control of autoimmune diseases.

Original languageEnglish
Pages (from-to)3653-3669
Number of pages17
JournalMolecular and Cellular Biology
Volume31
Issue number17
DOIs
Publication statusPublished - 2011 Sep

Fingerprint

Interleukin-17
Autoimmunity
Calcitriol Receptors
T-Lymphocytes
Vitamin D
Autoimmune Diseases
Core Binding Factor Alpha 2 Subunit
NFATC Transcription Factors
Histone Deacetylases
Autoimmune Experimental Encephalomyelitis
Chromatin Immunoprecipitation
Paralysis
Multiple Sclerosis
Disease Progression
Immune System
Central Nervous System
Gels
1,25-dihydroxyvitamin D

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Joshi, S., Pantalena, L. C., Liu, X. K., Gaffen, S. L., Liu, H., Rohowsky-Kochan, C., ... Youssef, S. (2011). 1,25-Dihydroxyvitamin D 3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Molecular and Cellular Biology, 31(17), 3653-3669. https://doi.org/10.1128/MCB.05020-11

1,25-Dihydroxyvitamin D 3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. / Joshi, Sneha; Pantalena, Luiz Carlos; Liu, Xikui K.; Gaffen, Sarah L.; Liu, Hong; Rohowsky-Kochan, Christine; Ichiyama, Kenji; Yoshimura, Akihiko; Steinman, Lawrence; Christakos, Sylvia; Youssef, Sawsan.

In: Molecular and Cellular Biology, Vol. 31, No. 17, 09.2011, p. 3653-3669.

Research output: Contribution to journalArticle

Joshi, S, Pantalena, LC, Liu, XK, Gaffen, SL, Liu, H, Rohowsky-Kochan, C, Ichiyama, K, Yoshimura, A, Steinman, L, Christakos, S & Youssef, S 2011, '1,25-Dihydroxyvitamin D 3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A', Molecular and Cellular Biology, vol. 31, no. 17, pp. 3653-3669. https://doi.org/10.1128/MCB.05020-11
Joshi, Sneha ; Pantalena, Luiz Carlos ; Liu, Xikui K. ; Gaffen, Sarah L. ; Liu, Hong ; Rohowsky-Kochan, Christine ; Ichiyama, Kenji ; Yoshimura, Akihiko ; Steinman, Lawrence ; Christakos, Sylvia ; Youssef, Sawsan. / 1,25-Dihydroxyvitamin D 3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. In: Molecular and Cellular Biology. 2011 ; Vol. 31, No. 17. pp. 3653-3669.
@article{9c260a8ec2824fe48802170cd0c9968a,
title = "1,25-Dihydroxyvitamin D 3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A",
abstract = "A new class of inflammatory CD4 + T cells that produce interleukin-17 (IL-17) (termed Th17) has been identified, which plays a critical role in numerous inflammatory conditions and autoimmune diseases. The active form of vitamin D, 1,25-dihydroxyvitamin D 3 [1,25(OH) 2D 3], has a direct repressive effect on the expression of IL-17A in both human and mouse T cells. In vivo treatment of mice with ongoing experimental autoimmune encephalomyelitis (EAE; a mouse model of multiple sclerosis) diminishes paralysis and progression of the disease and reduces IL-17A-secreting CD4 + T cells in the periphery and central nervous system (CNS). The mechanism of 1,25(OH) 2D 3 repression of IL-17A expression was found to be transcriptional repression, mediated by the vitamin D receptor (VDR). Transcription assays, gel shifting, and chromatin immunoprecipitation (ChIP) assays indicate that the negative effect of 1,25(OH) 2D 3 on IL-17A involves blocking of nuclear factor for activated T cells (NFAT), recruitment of histone deacetylase (HDAC), sequestration of Runt-related transcription factor 1 (Runx1) by 1,25(OH) 2D 3/VDR, and a direct effect of 1,25(OH) 2D 3 on induction of Foxp3. Our results describe novel mechanisms and new concepts with regard to vitamin D and the immune system and suggest therapeutic targets for the control of autoimmune diseases.",
author = "Sneha Joshi and Pantalena, {Luiz Carlos} and Liu, {Xikui K.} and Gaffen, {Sarah L.} and Hong Liu and Christine Rohowsky-Kochan and Kenji Ichiyama and Akihiko Yoshimura and Lawrence Steinman and Sylvia Christakos and Sawsan Youssef",
year = "2011",
month = "9",
doi = "10.1128/MCB.05020-11",
language = "English",
volume = "31",
pages = "3653--3669",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "17",

}

TY - JOUR

T1 - 1,25-Dihydroxyvitamin D 3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A

AU - Joshi, Sneha

AU - Pantalena, Luiz Carlos

AU - Liu, Xikui K.

AU - Gaffen, Sarah L.

AU - Liu, Hong

AU - Rohowsky-Kochan, Christine

AU - Ichiyama, Kenji

AU - Yoshimura, Akihiko

AU - Steinman, Lawrence

AU - Christakos, Sylvia

AU - Youssef, Sawsan

PY - 2011/9

Y1 - 2011/9

N2 - A new class of inflammatory CD4 + T cells that produce interleukin-17 (IL-17) (termed Th17) has been identified, which plays a critical role in numerous inflammatory conditions and autoimmune diseases. The active form of vitamin D, 1,25-dihydroxyvitamin D 3 [1,25(OH) 2D 3], has a direct repressive effect on the expression of IL-17A in both human and mouse T cells. In vivo treatment of mice with ongoing experimental autoimmune encephalomyelitis (EAE; a mouse model of multiple sclerosis) diminishes paralysis and progression of the disease and reduces IL-17A-secreting CD4 + T cells in the periphery and central nervous system (CNS). The mechanism of 1,25(OH) 2D 3 repression of IL-17A expression was found to be transcriptional repression, mediated by the vitamin D receptor (VDR). Transcription assays, gel shifting, and chromatin immunoprecipitation (ChIP) assays indicate that the negative effect of 1,25(OH) 2D 3 on IL-17A involves blocking of nuclear factor for activated T cells (NFAT), recruitment of histone deacetylase (HDAC), sequestration of Runt-related transcription factor 1 (Runx1) by 1,25(OH) 2D 3/VDR, and a direct effect of 1,25(OH) 2D 3 on induction of Foxp3. Our results describe novel mechanisms and new concepts with regard to vitamin D and the immune system and suggest therapeutic targets for the control of autoimmune diseases.

AB - A new class of inflammatory CD4 + T cells that produce interleukin-17 (IL-17) (termed Th17) has been identified, which plays a critical role in numerous inflammatory conditions and autoimmune diseases. The active form of vitamin D, 1,25-dihydroxyvitamin D 3 [1,25(OH) 2D 3], has a direct repressive effect on the expression of IL-17A in both human and mouse T cells. In vivo treatment of mice with ongoing experimental autoimmune encephalomyelitis (EAE; a mouse model of multiple sclerosis) diminishes paralysis and progression of the disease and reduces IL-17A-secreting CD4 + T cells in the periphery and central nervous system (CNS). The mechanism of 1,25(OH) 2D 3 repression of IL-17A expression was found to be transcriptional repression, mediated by the vitamin D receptor (VDR). Transcription assays, gel shifting, and chromatin immunoprecipitation (ChIP) assays indicate that the negative effect of 1,25(OH) 2D 3 on IL-17A involves blocking of nuclear factor for activated T cells (NFAT), recruitment of histone deacetylase (HDAC), sequestration of Runt-related transcription factor 1 (Runx1) by 1,25(OH) 2D 3/VDR, and a direct effect of 1,25(OH) 2D 3 on induction of Foxp3. Our results describe novel mechanisms and new concepts with regard to vitamin D and the immune system and suggest therapeutic targets for the control of autoimmune diseases.

UR - http://www.scopus.com/inward/record.url?scp=80052387833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052387833&partnerID=8YFLogxK

U2 - 10.1128/MCB.05020-11

DO - 10.1128/MCB.05020-11

M3 - Article

VL - 31

SP - 3653

EP - 3669

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 17

ER -