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IFN-beta inhibits human Th17 cell differentiation.

Publication ,  Journal Article
Ramgolam, VS; Sha, Y; Jin, J; Zhang, X; Markovic-Plese, S
Published in: J Immunol
October 15, 2009

IFN-beta-1a has been used over the past 15 years as a primary therapy for relapsing-remitting multiple sclerosis (MS). However, the immunomodulatory mechanisms that provide a therapeutic effect against this CNS inflammatory disease are not yet completely elucidated. The effect of IFN-beta-1a on Th17 cells, which play a critical role in the development of the autoimmune response, has not been extensively studied in humans. We have investigated the effect of IFN-beta-1a on dendritic cells (DCs) and naive CD4(+)CD45RA(+) T cells derived from untreated MS patients and healthy controls in the context of Th17 cell differentiation. We report that IFN-beta-1a treatment down-regulated the expression of IL-1beta and IL-23p19 in DCs, whereas it induced the gene expression of IL-12p35 and IL-27p28. We propose that IFN-beta-1a-mediated up-regulation of the suppressor of cytokine signaling 3 expression, induced via STAT3 phosphorylation, mediates IL-1beta and IL-23 down-regulation, while IFN-beta-1a-induced STAT1 phosphorylation induces IL-27p28 expression. CD4(+)CD45RA(+) naive T cells cocultured with supernatants from IFN-beta-1a-treated DCs exhibited decreased gene expression of the Th17 cell markers retinoic acid-related orphan nuclear hormone receptor c (RORc), IL-17A, and IL-23R. A direct IFN-beta-1a treatment of CD45RA(+) T cells cultured in Th17-polarizing conditions also down-regulated RORc, IL-17A, and IL-23R, but up-regulated IL-10 gene expression. Studies of the mechanisms involved in the Th17 cell differentiation suggest that IFN-beta-1a inhibits IL-17 and induces IL-10 secretion via activated STAT1 and STAT3, respectively. IFN-beta's suppression of Th17 cell differentiation may represent its most relevant mechanism of selective suppression of the autoimmune response in MS.

Duke Scholars

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 15, 2009

Volume

183

Issue

8

Start / End Page

5418 / 5427

Location

United States

Related Subject Headings

  • Up-Regulation
  • T-Lymphocytes, Helper-Inducer
  • STAT3 Transcription Factor
  • STAT1 Transcription Factor
  • Receptors, Thyroid Hormone
  • Receptors, Retinoic Acid
  • Receptors, Interleukin
  • Receptors, CCR6
  • Phosphorylation
  • Nuclear Receptor Subfamily 1, Group F, Member 3
 

Citation

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Ramgolam, V. S., Sha, Y., Jin, J., Zhang, X., & Markovic-Plese, S. (2009). IFN-beta inhibits human Th17 cell differentiation. J Immunol, 183(8), 5418–5427. https://doi.org/10.4049/jimmunol.0803227
Ramgolam, Vinod S., Yonggang Sha, Jianping Jin, Xin Zhang, and Silva Markovic-Plese. “IFN-beta inhibits human Th17 cell differentiation.J Immunol 183, no. 8 (October 15, 2009): 5418–27. https://doi.org/10.4049/jimmunol.0803227.
Ramgolam VS, Sha Y, Jin J, Zhang X, Markovic-Plese S. IFN-beta inhibits human Th17 cell differentiation. J Immunol. 2009 Oct 15;183(8):5418–27.
Ramgolam, Vinod S., et al. “IFN-beta inhibits human Th17 cell differentiation.J Immunol, vol. 183, no. 8, Oct. 2009, pp. 5418–27. Pubmed, doi:10.4049/jimmunol.0803227.
Ramgolam VS, Sha Y, Jin J, Zhang X, Markovic-Plese S. IFN-beta inhibits human Th17 cell differentiation. J Immunol. 2009 Oct 15;183(8):5418–5427.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 15, 2009

Volume

183

Issue

8

Start / End Page

5418 / 5427

Location

United States

Related Subject Headings

  • Up-Regulation
  • T-Lymphocytes, Helper-Inducer
  • STAT3 Transcription Factor
  • STAT1 Transcription Factor
  • Receptors, Thyroid Hormone
  • Receptors, Retinoic Acid
  • Receptors, Interleukin
  • Receptors, CCR6
  • Phosphorylation
  • Nuclear Receptor Subfamily 1, Group F, Member 3