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

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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.

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Acknowledgments

We thank Yanhong Wang and Chunmei Fan for their excellent technical assistance. This work was funded by a grant from National Natural Science Foundation of China (No. 81001335).

Conflict of interest

The authors declare that they have no conflicts of interest.

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Author notes

    Authors and Affiliations

    1. Department of Clinical Immunology, Branch of Immune Cell Biology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi’an, 710032, Shaanxi Province, People’s Republic of China

      Zhaohui Zheng, Xueyi Li, Jin Ding, Yuan Feng, Jinlin Miao, Xing Luo, Zhenbiao Wu & Ping Zhu

    2. Department of Medical Teaching and Research Administration, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China

      Tao Liu

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    1. Zhaohui Zheng
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    Correspondence to Zhenbiao Wu or Ping Zhu.

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    Responsible Editor: Liwu Li.

    Z. Zheng, T. Liu and X. Li contributed equally to this work.

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    Zheng, Z., Liu, T., Li, X. et al. Kinetic changes of regulatory B10 cells in collagen-induced arthritis could be regulated by cytokines IFN-γ and TGF-β1. Inflamm. Res. 64, 637–645 (2015). https://doi.org/10.1007/s00011-015-0846-5

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    • DOI: https://doi.org/10.1007/s00011-015-0846-5

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