Interleukin-10 attenuation of collagen induced arthritis is associated with suppression of interleukin-17 and retinoid related orphan receptor gammat production in macrophages and repression of classically activated macrophages (Arthritis Research & Therapy)

IntroductionOur objective was to determine the signaling pathway of interleukin-10 (IL-10) for modulating interleukin-17 (IL-17) expression in macrophages and the importance of this mediation in collagen-induced arthritis (CIA). Methods: Interleukin-10 knockout (IL-10-/-) mice and wild type (WT) mice were immunized with Chicken type II collagen (CII) to induce arthritis. The expressions of IL-17 and retinoid related orphan receptor gammat (RORgammat) in macrophages and joint tissues of the IL-10-/- mice and WT mice were analyzed by enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (QT-PCR), and Western blotting. The F4/80 macrophages and positive IL-17-producing macrophages in synovial tissues of the mice were determined by immunohistochemistry. The populations of classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes were analyzed by flow cytometry. The expressions of genes associated with M1 and M2 makers were analyzed by QT-PCR. Results: Compared to WT mice, IL-10-/- mice exacerbated CIA development, which associated with increased production of T helper cell 17 (TH17)/T helper cell 1 (TH1) pro-inflammatory cytokines and CII-specific immunoglobulin G2a (IgG2a) antibody after CII immunization. Macrophages in IL-10-/- mice had increased amounts of IL-17 and RORgammat than those in WT mice with CIA. Immunofluorescence microscopy showed that the number of IL-17-producing macrophages in synovial tissues were significantly higher in IL-10-/- mice than in WT mice. IL-10 deficiency might promote macrophage polarization towards the pro-inflammatory M1 phenotype that contributes to rheumatoid arthritis (RA) inflammation response. Conclusion: IL-10 inhibits IL-17 and RORgammat expression in macrophages and suppresses macrophages towards the pro-inflammatory M1 phenotype, which is important for IL-10 to mediate the pathogenesis of CIA.