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Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin.

Publication ,  Journal Article
Shinohara, ML; Kim, J-H; Garcia, VA; Cantor, H
Published in: Immunity
July 18, 2008

Mechanisms that prevent inappropriate or excessive interleukin-17-producing T helper (Th17) cell responses after microbial infection may be necessary to avoid autoimmunity. Here, we define a pathway initiated by engagement of type I IFN receptor (IFNAR) expressed by dendritic cells (DC) that culminated in suppression of Th17 cell differentiation. IFNAR-dependent inhibition of an intracellular translational isoform of Osteopontin, termed Opn-i, derepressed interleukin-27 (IL-27) secretion and prevented efficient Th17 responses. Moreover, Opn-i expression in DC and microglia regulated the type and intensity of experimental autoimmune encephalomyelitis (EAE). Mice containing DC deficient in Opn-i produced excessive amounts of IL-27 and developed a delayed disease characterized by an enhanced Th1 response compared with the dominant Th17 response of Opn-sufficient mice. Definition of the IFNAR-Opn-i axis that controls Th17 development provides insight into regulation of Th cell sublineage development and the molecular basis of type I interferon therapy for MS and other autoimmune diseases.

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

July 18, 2008

Volume

29

Issue

1

Start / End Page

68 / 78

Location

United States

Related Subject Headings

  • T-Lymphocytes, Helper-Inducer
  • T-Lymphocyte Subsets
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptor, Interferon alpha-beta
  • Protein Processing, Post-Translational
  • Protein Isoforms
  • Osteopontin
  • Mice, Mutant Strains
  • Mice
  • Interleukin-17
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shinohara, M. L., Kim, J.-H., Garcia, V. A., & Cantor, H. (2008). Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity, 29(1), 68–78. https://doi.org/10.1016/j.immuni.2008.05.008
Shinohara, Mari L., June-Ho Kim, Virgilio A. Garcia, and Harvey Cantor. “Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin.Immunity 29, no. 1 (July 18, 2008): 68–78. https://doi.org/10.1016/j.immuni.2008.05.008.
Shinohara, Mari L., et al. “Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin.Immunity, vol. 29, no. 1, July 2008, pp. 68–78. Pubmed, doi:10.1016/j.immuni.2008.05.008.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

July 18, 2008

Volume

29

Issue

1

Start / End Page

68 / 78

Location

United States

Related Subject Headings

  • T-Lymphocytes, Helper-Inducer
  • T-Lymphocyte Subsets
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptor, Interferon alpha-beta
  • Protein Processing, Post-Translational
  • Protein Isoforms
  • Osteopontin
  • Mice, Mutant Strains
  • Mice
  • Interleukin-17