TNF-α blockade induces IL-10 expression in human CD4+ T cells

被引：0
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作者：
Hayley G. Evans
Urmas Roostalu
Gina J. Walter
Nicola J. Gullick
Klaus S. Frederiksen
Ceri A. Roberts
Jonathan Sumner
Dominique L. Baeten
Jens G. Gerwien
Andrew P. Cope
Frederic Geissmann
Bruce W. Kirkham
Leonie S. Taams
机构：
[1] Centre for Molecular and Cellular Biology of Inflammation (CMCBI),Division of Immunology
[2] Infection and Inflammatory Disease,Department of Clinical Immunology and Rheumatology
[3] King’s College London,Academic Department of Rheumatology
[4] Biopharmaceuticals Research Unit,Department of Rheumatology
[5] Inflammation Biology,undefined
[6] Novo Nordisk A/S,undefined
[7] Academic Medical Centre/University of Amsterdam,undefined
[8] King's College London,undefined
[9] Guy’s and St Thomas’ NHS Trust,undefined
[10] Present address: Nuffield Department of Clinical Neurosciences,undefined
[11] Weatherall Institute of Molecular Medicine,undefined
[12] John Radcliffe Hospital,undefined
[13] University of Oxford,undefined
[14] Oxford OX3 9DS,undefined
[15] UK,undefined
[16] Present address: Institute of Inflammation and Repair,undefined
[17] Michael Smith Bldg,undefined
[18] Oxford Road,undefined
[19] University of Manchester,undefined
[20] Manchester M13 9PL,undefined
[21] UK,undefined
[22] Present address: Department of Rheumatology,undefined
[23] King’s College Hospital NHS Trust,undefined
[24] London SE5 9RS,undefined
[25] UK,undefined
来源：
Nature Communications | / 5卷
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摘要：
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.
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