A Single Microorganism Epitope Attenuates the Development of Murine Autoimmune Arthritis: Regulation of Dendritic Cells the Mannose Receptor.

A single epitope of analog of the receptors for activated C kinase (LACK) from , the polypeptide LACK, is recognized by Vβ4/Vα8 T cells, and activate these cells that drives the subsequent T helper (Th)2 response. This study was undertaken to investigate the therapeutic potential of the LACK epitope in murine autoimmune arthritis models. To explore the influence of the LACK epitope on murine collagen antibody-induced arthritis, as well as its immunological mechanism, we vaccinated or treated mice with a LACK epitope expression plasmid or polypeptide. The effect of LACK epitope was then evaluated by clinical scores, histopathology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Using flow cytometry, we measured the subsets and maturity of CD11c dendritic cells (DCs), as well as T cell polarization, in co-culture experiments. We also measured cytokine gene expression and production. The murine macrophage-like cell line RAW264.7 was used to identify the receptor for the epitope. Vaccination or treatment of the mice with the LACK epitope expression plasmid or polypeptide ameliorated the severity of arthritis. qRT-PCR analysis revealed that the LACK epitope improved the balance of effector T cells in synovial tissue compared to that in untreated arthritis controls. Toll-like receptor (TLR) 4 expression was diminished by LACK. The epitope also influenced T cell polarization by regulating the differentiation, maturation, and functions of CD11c DCs and upregulating Jagged1 ligand expression. Blocking the mannose receptor (MR) significantly attenuated LACK epitope-induced macrophage activation. Our data indicate that vaccination or treatment with a single microorganism epitope, LACK, is a highly efficient therapy for murine autoimmune arthritis. The therapeutic effects are mediated by the regulation of the differentiation, maturation, and functions of DCs MR, resulting in the upregulation of Jagged1 expression and Th2 cell polarization. Our results demonstrate the therapeutic potential of the LACK epitope in rheumatoid arthritis.