title: Engulfment of activated apoptotic cells abolishes TGF-β-mediated immunoregulation via the induction of IL-6.
abstract: Phagocytosis of apoptotic cells (ACs) is usually a potent immunoregulatory signal but can also promote inflammation. In this article, we show that administration of apoptotic dendritic cells (DCs) inhibited inflammation in vivo through increasing production of TGF-β from intrinsic DCs and B cells. However, ACs derived from LPS-activated DCs failed to restrain inflammation because of a short-lived but marked IL-6 response, which abolished the increase in TGF-β. Inhibition of IL-6 restored the protective anti-inflammatory properties of aACs and the TGF-β response. DCs isolated from mice that had received resting but not activated ACs could transfer the suppression of inflammation to recipient mice. These transferred DCs stimulated B cell TGF-β production and relied on an intact B cell compartment to limit inflammation. These results highlight how the activation state of AC governs their ability to control inflammation through reciprocal regulation of IL-6 and TGF-β.
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London WC1E 6JF, United Kingdom.
authors.forename: Clare A
authors.initials: CA
authors.lastname: Notley
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London WC1E 6JF, United Kingdom.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Brown
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London WC1E 6JF, United Kingdom.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: McGovern
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London WC1E 6JF, United Kingdom.
authors.forename: Christine K
authors.initials: CK
authors.lastname: Jordan
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London WC1E 6JF, United Kingdom m.ehrenstein@ucl.ac.uk.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ehrenstein
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001169:Arthritis, Experimental; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010587:Phagocytosis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D016212:Transforming Growth Factor beta