Toll‐like receptor 2 and 4 induced interleukin‐19 dampens immune reactions and associates inversely with spondyloarthritis disease activity

Summary 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 ( PBMC s) from healthy controls ( HC s) and in PBMC s and synovial fluid mononuclear cells ( SFMC s) from SpA patients. Further, we measured IL ‐19 in plasma from HC s and in plasma and synovial fluid from SpA patients. Constitutive IL ‐19 expression was present in both PBMC s and SFMC s and the secretion of IL ‐19 was increased by TLR‐2 and TLR‐4 ligands. Neutralizing IL ‐19 in HC PBMC s and SpA SFMC s 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 SFMC s produced less IL ‐19 in response to LPS compared with HC PBMC s. 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 .