Nature immunology, 2013-01, Vol.14 (1), p.72-81
2013
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Details
- Autor(en) / Beteiligte
- Titel
- The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90
- Ist Teil von
- Nature immunology, 2013-01, Vol.14 (1), p.72-81
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Act1 is an essential adaptor in interleukin 17 (IL-17)-mediated signaling and is recruited to the receptor for IL-17 after stimulation with IL-17. Here we found that Act1 was a 'client' protein of the molecular chaperone hsp90. The D10N variant of Act1 (Act1(D10N)) that is linked to susceptibility to psoriasis was defective in its interaction with hsp90, which resulted in a global loss of Act1 function. Act1-deficient mice modeled the mechanistic link between loss of Act1 function and susceptibility to psoriasis. Although Act1 was necessary for IL-17-mediated inflammation, Act1-deficient mice had a hyperactive response of the T(H)17 subset of helper T cells and developed spontaneous IL-22-dependent skin inflammation. In the absence of IL-17 signaling, IL-22 was the main contributor to skin inflammation, which provides a molecular mechanism for the association of Act1(D10N) with psoriasis susceptibility.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1529-2908eISSN: 1529-2916DOI: 10.1038/ni.2479Titel-ID: cdi_pubmed_primary_23202271
- Format
- –
- Schlagworte
- Animals, Cell Line, Connexin 43 - genetics, Connexin 43 - immunology, Connexin 43 - metabolism, Disease Models, Animal, Genetic Predisposition to Disease, HSP90 Heat-Shock Proteins - metabolism, Humans, Interleukin-17 - metabolism, Mice, Mice, Knockout, Molecular Chaperones - genetics, Molecular Chaperones - metabolism, Mutation - genetics, Peptide Fragments - genetics, Peptide Fragments - immunology, Peptide Fragments - metabolism, Polymorphism, Genetic, Protein Binding - genetics, Protein Binding - immunology, Psoriasis - genetics, Psoriasis - immunology, Signal Transduction, Th17 Cells - immunology