Anti-inflammatory role of APRIL by modulating regulatory B cells in antigen-induced arthritis
APRIL (A Proliferation-Inducing Ligand) acts as a secreted factor and plays important roles in B cell biology and chronic inflammation. The reported capacity of APRIL to stimulate B cells in vitro raised the hypothesis that APRIL may be a disease promoter in autoimmune diseases such as rheumatoid arthritis. In contrast, there is large evidence that B Lymphocyte Stimulator Factor (BAFF) can break B cell tolerance in mice and humans. This study was undertaken to examine the ability of APRIL to regulate B cell-mediated inflammatory response in a model of antigen-induced arthritis (AIA) in mice. AIA was induced by administration of antigen (mBSA) into the knee joints of previously immunized APRIL-transgenic (Tg) mice and their littermates. Flow cytometry was used to analyze the different inflammatory cell populations in spleen and draining lymph nodes in acute and chronic disease, while cytokine levels were assessed by ELISA. In the acute stage of disease APRIL-Tg mice displayed a decrease in joint swelling, disease score and inflammatory infiltrate in articular tissues, as compared with their littermates. In addition, we observed a decrease of cellularity in draining lymph nodes of APRIL-Tg mice. Flow cytometry analysis revealed an increase of CD19+IgM+CD5+ cell population in draining lymph nodes and increase of CD19+CD21hiCD23hi (B regulatory) cells in APRIL-Tg mice with arthritis and, increase of IL-10 and CXCL13 production in vitro.