Journal
IMMUNITY
Volume 29, Issue 1, Pages 68-78Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2008.05.008
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Funding
- NCI NIH HHS [T32 CA70083, T32 CA070083] Funding Source: Medline
- NIAID NIH HHS [AI 12184, R01 AI048125-05, R37 AI012184, R01 AI048125, R37 AI012184-31, AI 48125] Funding Source: Medline
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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, dere-pressed 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 sub-lineage development and the molecular basis of type I interferon therapy for MS and other autoimmune diseases.
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