Methods: Bone marrow derived macrophages and dendritic cells from CX3CR1GFP/+/RAG-1-/- animals and IL-19 expression was determined. To investigate the role of commensal microorganisms on IL-19 and on the type I IL‑20 receptor (formed by the IL-20 receptor alpha (IL-20RA) and beta (IL‑20RB) subunits) expression levels were determined in mice with different hygiene statuses.
Results: CX3CR1-positive macrophages produced significantly more IL-19 than dendritic cells. IL-19 expression was further up-regulated after stimulation with Toll-like receptor ligands. Macrophages expressed IL-20RB but not IL-20RA. IL-19 did not induce an activation of macrophages in an autocrine fashion. In intestinal tissues of non-diseased mice, we did not detect IL-19 expression during steady state conditions. IL-19 expression was only found in mesenteric lymph nodes, but not in peripheral lymph nodes, skin, liver, spleen, stomach small and large intestine. In contrast intestinal inflammation lead to the expression of IL-19 by phagocytes isolated from the large intestine of mice with colitis. IL‑20RB was expressed in all investigated organs with the highest expression in the skin. Expression of IL-20RA was found in the epidermis, the stomach and proximal colon but not in the small intestine.
Conclusions: CX3CR1-positive macrophages are a cellular source of IL-19 acting on mucosal sites where the type I IL-20 receptor is expressed to maintain homeostasis on inner and outer body surfaces.