title: Toll-like receptor 2 and 4 induced interleukin-19 dampens immune reactions and associates inversely with spondyloarthritis disease activity.
abstract: Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases affecting joints, gut, skin and entheses. The inflammatory process involves activation of Toll-like receptor (TLR)-2 and TLR-4 and production of cytokines and chemokines such as monocyte chemoattractant protein 1 (CCL2/MCP-1). This proinflammatory chemokine recruits monocytes to sites of inflammation and is central in the development of several immune-mediated inflammatory diseases. Interleukin (IL)-19 is a member of the IL-10 family of cytokines. IL-19-deficient mice are more susceptible to innate-mediated colitis and develop more severe inflammation in response to injury. In this work, we studied inducers of IL-19 production and effect of IL-19 on the production of CCL2/MCP-1 and proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) and in PBMCs and synovial fluid mononuclear cells (SFMCs) from SpA patients. Further, we measured IL-19 in plasma from HCs and in plasma and synovial fluid from SpA patients. Constitutive IL-19 expression was present in both PBMCs and SFMCs and the secretion of IL-19 was increased by TLR-2 and TLR-4 ligands. Neutralizing IL-19 in HC PBMCs and SpA SFMCs resulted in increased production of CCL-2/MCP-1. IL-19 concentrations were decreased in synovial fluid compared with plasma and associated inversely with disease activity in SpA. SpA SFMCs produced less IL-19 in response to LPS compared with HC PBMCs. These findings indicate that IL-19 production is diminished in SpA. Taken together, impaired IL-19 control of the innate immune system might be involved in the pathogenesis of SpA.
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors: T W
authors: TW
authors: Kragstrup
authors: T
authors: T
authors: Andersen
authors: C
authors: C
authors: Holm
authors: B
authors: B
authors: Schiøttz-Christensen
authors: A G
authors: AG
authors: Jurik
authors: M
authors: M
authors: Hvid
authors: B
authors: B
authors: Deleuran
mesh_terms: D000328:Adult; D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007378:Interleukins / Q000097:blood / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000276:immunology* / Q000473:pathology; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000097:blood / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000097:blood / Q000276:immunology*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C421250:IL19 protein, human; D007378:Interleukins; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: IL-10; IL-19; Toll-like receptor; innate immunity; spondylitis
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