D1.416 - Regulatory T Cells Induced by B cells Decreased Osteoclast Activity and Alleviated Disease Severity of Collagen Antibody Induced Arthritis

Inflammation plays a critical role in the pathogenesis of rheumatoid arthritis. Defective regulatory T (Treg) cells might contribute to increased levels of inflammatory cytokines that enhance osteoclast-mediated bone resorption in rheumatoid arthritis. Our studies have shown that the specific Treg cells induced by B cells (Treg-of-B cells) exert the ability to suppress T cell proliferation and secrete high levels of the inhibitory cytokine interleukin-10 (IL-10). In this study, we investigated whether Treg-of-B cells affect the activation of osteoclast cells and evaluated their therapeutic effects of Treg-of B cells in a collagen antibody-induced arthritis (CAIA) animal model.

 In vitro, Treg-of-B cells were generated from splenic T cells following B cell and antibody induction. Osteoclast progenitor cells were generated from the bone marrow in the femurs and tibias, then cultured with Treg-of-B cells. The expression of osteoclast-related genes, cytokines, and signaling proteins was determined using real-time PCR, ELISA assay, and western blotting, respectively. In vivo, Treg-of-B cells were delivered intravenously to CAIA mice to evaluate the effect on disease severity. 

Treg-of-B cells regulate the maturation of osteoclast progenitor cells through the ICOS and LAG-3 pathways. Application of Treg-of-B cells decreased the clinical scores and the levels of inflammatory cytokines. Furthermore, Treg-of-B cell treatment increased IL-10 production and the percentage of Foxp3⁺-expressing T cells in local lymph nodes.

Treg-of-B cells influence osteoclast maturation and decrease disease severity of CAIA, which might become a novel therapeutic approach for rheumatoid arthritis.