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Immunity. 2008 Jul 18;29(1):68-78. doi: 10.1016/j.immuni.2008.05.008.

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

Author information

1
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.

Abstract

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.

PMID:
18619869
PMCID:
PMC2625293
DOI:
10.1016/j.immuni.2008.05.008
[Indexed for MEDLINE]
Free PMC Article

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