Nature communications, 2017-01, Vol.8 (1), p.13946-13946, Article 13946
2017
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Details
- Autor(en) / Beteiligte
- Titel
- The transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction
- Ist Teil von
- Nature communications, 2017-01, Vol.8 (1), p.13946-13946, Article 13946
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Mutations of DOCK8 in humans cause a combined immunodeficiency characterized by atopic dermatitis with high serum IgE levels. However, the molecular link between DOCK8 deficiency and atopic skin inflammation is unknown. Here we show that CD4 T cells from DOCK8-deficient mice produce large amounts of IL-31, a major pruritogen associated with atopic dermatitis. IL-31 induction critically depends on the transcription factor EPAS1, and its conditional deletion in CD4 T cells abrogates skin disease development in DOCK8-deficient mice. Although EPAS1 is known to form a complex with aryl hydrocarbon receptor nuclear translocator (ARNT) and control hypoxic responses, EPAS1-mediated Il31 promoter activation is independent of ARNT, but in collaboration with SP1. On the other hand, we find that DOCK8 is an adaptor and negative regulator of nuclear translocation of EPAS1. Thus, EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction in CD4 T cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/ncomms13946Titel-ID: cdi_doaj_primary_oai_doaj_org_article_d905189145bf4be9a4491bbce9d00563
- Format
- –
- Schlagworte
- Active Transport, Cell Nucleus, Animals, Antigens, Aryl Hydrocarbon Receptor Nuclear Translocator - genetics, Aryl Hydrocarbon Receptor Nuclear Translocator - immunology, Basic Helix-Loop-Helix Transcription Factors - deficiency, Basic Helix-Loop-Helix Transcription Factors - genetics, Basic Helix-Loop-Helix Transcription Factors - immunology, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - pathology, Cell Nucleus - immunology, Cell Nucleus - metabolism, Collaboration, Cytokines, Cytosol - immunology, Cytosol - metabolism, Dermatitis, Dermatitis, Atopic - genetics, Dermatitis, Atopic - immunology, Dermatitis, Atopic - pathology, Disease Models, Animal, Female, Gene Expression Regulation, Guanine Nucleotide Exchange Factors - deficiency, Guanine Nucleotide Exchange Factors - genetics, Guanine Nucleotide Exchange Factors - immunology, Heterozygote, Hydrocarbons, Immunoglobulin E - genetics, Immunoglobulin E - immunology, Interleukins - genetics, Interleukins - immunology, Lymphocytes, Male, Mice, Mice, Knockout, Mutation, Peptides, Promoter Regions, Genetic, Protein Transport, Pruritus, Signal Transduction, Skin diseases, Sp1 Transcription Factor - genetics, Sp1 Transcription Factor - immunology, Transcription factors