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Inflammation Research

, Volume 64, Issue 8, pp 637–645 | Cite as

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

  • Zhaohui Zheng
  • Tao Liu
  • Xueyi Li
  • Jin Ding
  • Yuan Feng
  • Jinlin Miao
  • Xing Luo
  • Zhenbiao WuEmail author
  • Ping ZhuEmail author
Original Research Paper

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.

Keywords

Regulatory B10 cells Regulation Arthritis IFN-γ TGF-β1 

Notes

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.

References

  1. 1.
    Klareskog L, Catrina A, Paget S. Rheumatoid Arthritis. Lancet. 2009;373:659–72.PubMedCrossRefGoogle Scholar
  2. 2.
    Nakken B, Munthe LA, Konttinen YT, Sandberg AK, Szekanecz Z, Alex P, et al. B-cells and their targeting in rheumatoid arthritis—current concepts and future perspectives. Autoimmun Rev. 2011;11:28–34.PubMedCrossRefGoogle Scholar
  3. 3.
    Reddy V, Croca S, Gerona D, De La Torre I, Isenberg D, McDonald V, et al. Serum rituximab levels and efficiency of B cell depletion: differences between patients with rheumatoid arthritis and systemic lupus erythematosus. Rheumatology. 2013;52:951–2.PubMedCrossRefGoogle Scholar
  4. 4.
    Bredemeier M, Oliveira FK, Rocha CM. Low-versus high-dose Rituximab for Rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res. 2014;66:228–35.CrossRefGoogle Scholar
  5. 5.
    Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, et al. Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol. 2007;178:7868–78.PubMedCrossRefGoogle Scholar
  6. 6.
    Mauri C, Gray D, Mushtaq N, Londei M. Prevention of arthritis by interleukin 10-producing B cells. J Exp Med. 2003;197:489–501.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Neta R, Salvin S. Specific suppression of delayed hypersensitivity: the possible presence of a suppressor B cell in the regulation of delayed hypersensitivity. J Immunol. 1974;113:1716–25.PubMedGoogle Scholar
  8. 8.
    Matsushita T, Horikawa M, Iwata Y, Tedder TF. Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. J Immunol. 2010;185:2240–52.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K, et al. Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol. 2010;184:4801–9.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Yang M, Sun L, Wang S, Ko K-H, Xu H, Zheng B-J, et al. Cutting edge: novel function of B cell-activating factor in the induction of IL-10-producing regulatory B cells. J Immunol. 2010;184:3321–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Yang M, Deng J, Liu Y, Ko K-H, Wang X, Jiao Z, et al. IL-10–producing regulatory B10 cells ameliorate collagen-induced arthritis via suppressing Th17 cell generation. Am J Pathol. 2012;180:2375–85.PubMedCrossRefGoogle Scholar
  12. 12.
    Llorente L, Richaud-Patin Y, Fior R, Alcocer-Varela J, Wijdenes J, Fourrier BM, et al. In vivo production of interleukin-10 by non-t cells in rheumatoid arthritis, Sjöugren’s syndrome, and systemic lupus erythematosus. Arthritis Rheum. 1994;37:1647–55.PubMedCrossRefGoogle Scholar
  13. 13.
    Iwata Y, Matsushita T, Horikawa M, DiLillo DJ, Yanaba K, Venturi GM, et al. Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood. 2011;117:530–41.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Ma L, Liu B, Jiang Z, Jiang Y. Reduced numbers of regulatory B cells are negatively correlated with disease activity in patients with new-onset rheumatoid arthritis. Clin Rheumatol. 2014;33:187–95.PubMedCrossRefGoogle Scholar
  15. 15.
    Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein MR, Isenberg DA, et al. CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med. 2013;5:173ra23–173ra23.PubMedCrossRefGoogle Scholar
  16. 16.
    Krausz S, Garcia S, Ambarus CA, de Launay D, Foster M, Naiman B, et al. Angiopoietin-2 promotes inflammatory activation of human macrophages and is essential for murine experimental arthritis. Ann Rheum Dis. 2012;71:1402–17.PubMedCrossRefGoogle Scholar
  17. 17.
    Garcia G, Komagata Y, Slavin AJ, Maron R, Weiner HL. Suppression of collagen-induced arthritis by oral or nasal administration of type II collagen. J Autoimmun. 1999;13:315–24.PubMedCrossRefGoogle Scholar
  18. 18.
    Sims NA, Green JR, Glatt M, Schlict S, Martin TJ, Gillespie MT, et al. Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen-induced arthritis. Arthritis Rheum. 2004;50:2338–46.PubMedCrossRefGoogle Scholar
  19. 19.
    Joosten LA, Lubberts E, Durez P, Helsen M, Jacobs MJ, Goldman M, et al. Role of interleukin-4 and interleukin-10 in murine collagen-induced arthritis. Protective effect of interleukin-4 and interleukin-10 treatment on cartilage destruction. Arthritis Rheum. 1997;40:249–60.PubMedCrossRefGoogle Scholar
  20. 20.
    DiLillo DJ, Griffiths R, Seshan SV, Magro CM, Ruiz P, Coffman TM, et al. B lymphocytes differentially influence acute and chronic allograft rejection in mice. J Immunol. 2011;186:2643–54.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Smith SH, Tedder TF. Targeting B-cells mitigates autoimmune diabetes in NOD mice: what is plan b? Diabetes. 2009;58:1479–81.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Cantaert T, Doorenspleet ME, FrancoSalinas G, Paramarta JE, Klarenbeek PL, Tiersma Y, et al. Increased numbers of CD5+ B lymphocytes with a regulatory phenotype in spondyloarthritis. Arthritis Rheum. 2012;64:1859–68.PubMedCrossRefGoogle Scholar
  23. 23.
    Blair PA, Noreña LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, et al. CD19(+) CD24 (hi) CD38 (hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity. 2010;32:129–40.PubMedCrossRefGoogle Scholar
  24. 24.
    Zha B, Wang L, Liu X, Liu J, Chen Z, Xu J, et al. Decrease in proportion of CD19+ CD24hiCD27+ B cells and impairment of their suppressive function in Graves Disease. PLoS One. 2012;7:e49835.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Li X, Zhong H, Bao W, Boulad N, Evangelista J, Haider MA, et al. Defective regulatory B-cell compartment in patients with immune thrombocytopenia. Blood. 2012;120:3318–25.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Alex P, Szodoray P, Knowlton N, Dozmorov I, Turner M, Frank M, et al. Multiplex serum cytokine monitoring as a prognostic tool in rheumatoid arthritis. Clin Exp Rheumatol. 2007;25:584.PubMedGoogle Scholar
  27. 27.
    Gaffen SL. Recent advances in the IL-17 cytokine family. Curr Opin Immunol. 2011;23:613–9.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Oranskii S, Eliseeva L, Khanfetian R. Body structure and serum concentration of adiponectin and cytokines (IL-6, -10 and TNF-alpha) in rheumatoid arthritis combined with obesity. Voprosy Pitaniia. 2013;82:10–4.PubMedGoogle Scholar
  29. 29.
    Zhang W, Cong X-L, Qin Y-H, He Z-W, He D-Y, Dai S-M. IL-18 upregulates the production of key regulators of osteoclastogenesis from fibroblast-like synoviocytes in rheumatoid arthritis. Inflammation. 2013;36:103–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Kelchtermans H, Schurgers E, Geboes L, Mitera T, Van Damme J, Van Snick J, et al. Effector mechanisms of interleukin-17 in collagen-induced arthritis in the absence of interferon-gamma and counteraction by interferon-gamma. Arthritis Res Ther. 2009;11:R122.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Thornton S, Duwel LE, Boivin GP, Ma Y, Hirsch R. Association of the course of collagen-induced arthritis with distinct patterns of cytokine and chemokine messenger RNA expression. Arthritis Rheum. 1999;42:1109–18.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Zhaohui Zheng
    • 1
  • Tao Liu
    • 2
  • Xueyi Li
    • 1
  • Jin Ding
    • 1
  • Yuan Feng
    • 1
  • Jinlin Miao
    • 1
  • Xing Luo
    • 1
  • Zhenbiao Wu
    • 1
    Email author
  • Ping Zhu
    • 1
    Email author
  1. 1.Department of Clinical Immunology, Branch of Immune Cell Biology, State Key Discipline of Cell Biology, Xijing HospitalFourth Military Medical UniversityXi’anPeople’s Republic of China
  2. 2.Department of Medical Teaching and Research Administration, Xijing HospitalFourth Military Medical UniversityXi’anPeople’s Republic of China

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