Journal
JOURNAL OF IMMUNOLOGY
Volume 188, Issue 11, Pages 5319-5326Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1101044
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Funding
- University of Salzburg
- Austrian Fond zur Forderung der Wissenschaftlichen Forschung [P22202]
- Austrian Academy of Sciences at the Department of Molecular Biology, University of Salzburg
- Austrian Science Fund (FWF) [P 22202] Funding Source: researchfish
- Austrian Science Fund (FWF) [W1213, P22202] Funding Source: Austrian Science Fund (FWF)
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IL-31 is a T cell-derived cytokine that signals via a heterodimeric receptor composed of IL-31R alpha and oncostatin M receptor beta. Although several studies have aimed to investigate IL-31 mediated effects, the biological functions of this cytokine are currently not well understood. IL-31 expression correlates with the expression of IL-4 and IL-13 and is associated with atopic dermatitis in humans, indicating that IL-31 is involved in Th2-mediated skin inflammation. Because dendritic cells are the main activators of Th cell responses, we posed the question of whether dendritic cells express the IL-31R complex and govern immune responses triggered by IL-31. In the current study, we report that primary human CD1c(+) as well as monocyte-derived dendritic cells significantly upregulate the IL-31R alpha receptor chain upon stimulation with IFN-gamma. EMSAs, chromatin immunoprecipitation assays, and small interfering RNA-based silencing assays revealed that STAT1 is the main transcription factor involved in IFN-gamma dependent IL-31R alpha expression. Subsequent IL-31 stimulation resulted in a dose-dependent release of proinflammatory mediators, including TNF-alpha, IL-6, CXCL8, CCL2, CCL5, and CCL22. Because these cytokines are crucially involved in skin inflammation, we hypothesize that IL-31 specific activation of dendritic cells may be part of a positive feedback loop driving the progression of inflammatory skin diseases. The Journal of Immunology, 2012, 188: 5319-5326.
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