Kinetic changes of regulatory B10 cells in collagen-induced arthritis could be regulated by cytokines IFN-γ and TGF-β1

Abstract

Objective: The status of B10 cells in patients with rheumatoid arthritis (RA) has not been consistently reported. In this study, we observed the kinetic changes of the B10 cells in collagen-induced arthritis (CIA) mice and the influence of multiple cytokines on the B10 cells to investigate the potential mechanism underlying the changes of B10 cells. Methods: The kinetic changes of frequency and function of the CD19+CD1dhiCD5+ cells in splenic cells were observed during the complete progress of CIA mice. The kinetic changes of cytokines IL-4, IL-6, IL-17A, IL-18, TNF-α, IFN-γ and TGF-β1 were also detected. Then influence of these cytokines on the status of B10 cells was investigated both in vitro and in vivo. Results: The frequency and suppressive ability of the CD19+CD1dhiCD5+ cells increased to its peak on the 14th day while gradually decreased subsequently. IFN-γ showed a similar tendency with the CD19+CD1dhiCD5+ cells, whereas IL-6, IL-17A, IL-18, TNF-α, and TGF-β1 reached its peak on the 28–35th day. In addition, IFN-γ up-regulated while TGF-β1 down-regulated the frequency and function of the CD19+CD1dhiCD5+ cells both in vitro and in vivo. Conclusion: The B10 cells in CIA mice could be regulated by IFN-γ and TGF-β1, suggesting that the status of B10 cells in RA may be influenced by the balance of pro-inflammatory and anti-inflammatory factors, and the impaired B10 cells could be recovered in vitro by adequate treatment before being used for a therapeutic method in clinical practice.