AUTHOR=Yang Fan , Fan Xuemei , Huang He , Dang Qiujie , Lei Hongwei , Li Yang 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01528

DOI=10.3389/fimmu.2018.01528

ISSN=1664-3224

ABSTRACT=A single epitope of Leishmania analogue of the receptors for activated C kinase (LACK) from Leishmania major, the polypeptide LACK156-173, is recognized by Vβ4+/Vα8+ T cells, and activate these cells that drives the subsequent Th2 response. This study was undertaken to investigate the therapeutic potential of the LACK156-173 epitope in murine autoimmune arthritis models. To explore the influence of the LACK156-173 epitope on murine collagen antibody-induced arthritis, as well as its immunological mechanism, we vaccinated or treated mice with a LACK156-173 epitope expression plasmid or polypeptide. The effect of LACK156-173 epitope was then evaluated by clinical scores, histopathology, and 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 LACK156-173 epitope expression plasmid or polypeptide ameliorated the severity of arthritis. qRT-PCR analysis revealed that the LACK156-173 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 LACK156-173. The epitope also influenced T cell polarization by regulating the differentiation, maturation, and functions of CD11c+ DCs and up-regulating Jagged1 ligand expression. Blocking the mannose receptor (MR) significantly attenuated LACK156-173 epitope-induced macrophage activation. Our data indicate that vaccination or treatment with a single microorganism epitope, LACK156-173, 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 via MR, resulting in the up-regulation of Jagged1 expression and Th2 cell polarization. Our results demonstrate the therapeutic potential of the LACK156-173 epitope in rheumatoid arthritis.