TNF-α blockade induces IL-10 expression in human CD4+ T cells
| Autor: | Andrew P. Cope, Hayley G. Evans, Urmas Roostalu, Ceri A. Roberts, Leonie S. Taams, Gina J Walter, Nicola J. Gullick, Jens Gerwien, Dominique Baeten, Frederic Geissmann, Jonathan Sumner, Bruce Kirkham, Klaus Stensgaard Frederiksen |
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| Přispěvatelé: | AII - Amsterdam institute for Infection and Immunity, Clinical Immunology and Rheumatology |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_treatment
Interleukin-1beta Molecular Sequence Data General Physics and Astronomy chemical and pharmacologic phenomena General Biochemistry Genetics and Molecular Biology Article Pathogenesis Arthritis Rheumatoid Ikaros Transcription Factor Mice Dogs Sequence Homology Nucleic Acid Gene expression medicine Animals Humans Transcription factor Cells Cultured Conserved Sequence Multidisciplinary Base Sequence Chemistry Tumor Necrosis Factor-alpha hemic and immune systems General Chemistry IKZF3 Molecular biology Blockade Interleukin-10 Rats Interleukin 10 Cytokine Antirheumatic Agents Case-Control Studies Immunology Th17 Cells Tumor necrosis factor alpha Cattle |
| Zdroj: | Nature communications, 5. Nature Publishing Group Nature communications |
| DOI: | 10.1038/ncomms4199 |
| Popis: | IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells. |
| Databáze: | OpenAIRE |
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