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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shinohara, ML; Kim, J-H; Garcia, VA; Cantor, H

Published Date

  • July 18, 2008

Published In

Volume / Issue

  • 29 / 1

Start / End Page

  • 68 - 78

PubMed ID

  • 18619869

Pubmed Central ID

  • 18619869

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2008.05.008

Language

  • eng

Conference Location

  • United States