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Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia
- Source :
- Nature Communications. 3
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- Interleukin-17A, the prototypical member of the interleukin-17 cytokine family, coordinates local tissue inflammation by recruiting neutrophils to sites of infection. Dysregulation of interleukin-17 signalling has been linked to the pathogenesis of inflammatory diseases and autoimmunity. The interleukin-17 receptor family members (A-E) have a broad range of functional effects in immune signalling yet no known role has been described for the remaining orphan receptor, interleukin-17 receptor D, in regulating interleukin-17A-induced signalling pathways. Here we demonstrate that interleukin-17 receptor D can differentially regulate the various pathways employed by interleukin-17A. Neutrophil recruitment, in response to in vivo administration of interleukin-17A, is abolished in interleukin-17 receptor D-deficient mice, correlating with reduced interleukin-17A-induced activation of p38 mitogen-activated protein kinase and expression of the neutrophil chemokine MIP-2. In contrast, interleukin-17 receptor D deficiency results in enhanced interleukin-17A-induced activation of nuclear factor-kappa B and interleukin-6 and keratinocyte chemoattractant expression. Interleukin-17 receptor D disrupts the interaction of Act1 and TRAF6 causing differential regulation of nuclear factor-kappa B and p38 mitogen-activated protein kinase signalling pathways.
- Subjects :
- General Physics and Astronomy
Electrophoretic Mobility Shift Assay
Enzyme-Linked Immunosorbent Assay
C-C chemokine receptor type 6
Biology
p38 Mitogen-Activated Protein Kinases
General Biochemistry, Genetics and Molecular Biology
Mice
Estrogen-related receptor alpha
Cell Line, Tumor
Animals
Humans
SOCS2
Nuclear receptor co-repressor 1
Mice, Knockout
TNF Receptor-Associated Factor 6
Orphan receptor
Receptors, Interleukin-17
Multidisciplinary
Interleukin-6
Interleukin-17
General Chemistry
Peptide Fragments
Neuron-derived orphan receptor 1
Cell biology
Neutrophil Infiltration
Connexin 43
Interleukin-21 receptor
ROR1
HeLa Cells
Signal Transduction
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....5eef8f4163fab36b738e1e42af231725