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Changes of Treg/Th17 Ratio in Spleen of Acute Gouty Arthritis Rat Induced by MSU Crystals

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Abstract

Acute gouty arthritis is the inflammation of joint tissues in the acute form due to the deposition of monosodium urate (MSU) crystals. Regulatory T cells (Tregs) and Th17 cells play an important role in the development and progression of inflammatory diseases. However, the expression and role of Tregs and Th17 cells are not clear in this disease. Here, we investigated the changes of Tregs, Th17 cells, and Treg/Th17 ratio in spleen, as well as the inflammatory cytokines in blood and joint tissue pathology in acute gouty arthritis rat induced by MSU. We found that both the percentages of Tregs and Th17 cells in spleen increased at an early stage (6 h). Tregs decreased at 12 and 24 h, and rise again at 48 and 72 h. However, Th17 cells reached its peak at 24 h, and then decreased after 48 h. Treg/Th17 ratio showed an initial decrease and then increase, and further reached its minimum value at 24 h. But the ratios of Treg/Th17at all times were lower than that of normal control. The level of serum cytokines (IL-1β, IL-6, IL-17, TNF-α, and IL-10) showed an opposite trend to Treg/Th17 ratio, except the level of TGF-β1 was similar to Tregs. In summary, Tregs and Th17 cells in spleen changed over time during the development of acute gouty arthritis. Decrease of Treg/Th17 ratio was consistent with inflammation development in the joints, suggesting that Treg/Th17 imbalance may involve in pathogenesis of acute gouty arthritis.

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References

  1. Murunikkara, V., and M. Rasool. 2014. Trikatu, a herbal compound that suppresses monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Cell Biochemistry & Function 32 (1): 106–114.

    Article  CAS  Google Scholar 

  2. Schlesinger, N., and R.G. Thiele. 2010. The pathogenesis of bone erosions in gouty arthritis. Annals of the Rheumatic Diseases 69 (11): 1907–1912.

    Article  PubMed  CAS  Google Scholar 

  3. Sakaguchi, S., M. Miyara, C.M. Costantino, and D.A. Hafler. 2010. Foxp3+ regulatory T cells in the human immune system. Nature Reviews Immunology 10 (7): 490–500.

    Article  PubMed  CAS  Google Scholar 

  4. Piccirillo, C.A., E. D’Hennezel, E. Sgouroudis, and E. Yurchenko. 2008. Cd4+Foxp3+ regulatory T cells in the control of autoimmunity: in vivo veritas. Current Opinion in Immunology 20 (6): 655–662.

    Article  PubMed  CAS  Google Scholar 

  5. Rudensky, A.Y. 2011. Regulatory T cells and Foxp3. Immunological Reviews 241 (1): 260–268.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Zhou, L., J.E. Lopes, M.M. Chong, I.I. Ivanov, R. Min, G.D. Victora, et al. 2008. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453: 236–240.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Coderre, T.J., and P.D. Wall. 1987. Ankle joint urate arthritis (AJUA) in rats: an alternative animal model of arthritis to that produced by Freund’s adjuvant. Pain 28 (3): 379–393.

    Article  PubMed  CAS  Google Scholar 

  8. Park, J.S., Y. Oh, O. Park, C.A. Foss, S.M. Lim, D.G. Jo, et al. 2017. Pegylated trail ameliorates experimental inflammatory arthritis by regulation of Th17 cells and regulatory T cells. Journal of Controlled Release 267: 163–171.

    Article  PubMed  CAS  Google Scholar 

  9. Hartmann, P., A. Szabó, G. Eros, D. Gurabi, G. Horváth, I. Németh, et al. 2009. Anti-inflammatory effects of phosphatidylcholine in neutrophil leukocyte-dependent acute arthritis in rats. European Journal of Pharmacology 622 (1–3): 58–64.

    Article  PubMed  CAS  Google Scholar 

  10. Fasching, P., M. Stradner, W. Graninger, C. Dejaco, and J. Fessler. 2017. Therapeutic potential of targeting the Th17/Treg axis in autoimmune disorders. Molecules 22 (1): 134.

    Article  CAS  Google Scholar 

  11. An, N., Y. Chen, C. Wang, C. Yang, Z.H. Wu, J. Xue, et al. 2017. Chloroquine autophagic inhibition rebalances Th17/Treg-mediated immunity and ameliorates systemic lupus erythematosus. Cellular Physiology & Biochemistry 44 (1): 412–422.

    Article  CAS  Google Scholar 

  12. Pesce, B., L. Soto, F. Sabugo, P. Wurmann, M. Cuchacovich, M.N. López, et al. 2013. Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients. Clinical & Experimental Immunology 171 (3): 237–242.

    Article  CAS  Google Scholar 

  13. Tramontini, N., C. Huber, L.B. Ru, R.A. Terkeltaub, and K.S. Kilgore. 2004. Central role of complement membrane attack complex in monosodium urate crystal–induced neutrophilic rabbit knee synovitis. Arthritis & Rheumatology 50 (8): 2633–2639.

    Article  Google Scholar 

  14. Taylor, W.J., J. Fransen, T.L. Jansen, N. Dalbeth, H.R. Schumacher, M. Brown, et al. 2015. Study for updated gout classification criteria: identification of features to classify gout. Arthritis Care & Research 67 (9): 1304–1315.

    Article  Google Scholar 

  15. Nistala, K., H. Moncrieffe, K.R. Newton, H. Varsani, P. Hunter, and L.R. Wedderburn. 2008. Interleukin-17-producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. Arthritis & Rheumatology 58 (3): 875–887.

    Article  Google Scholar 

  16. Monte, K., C. Wilson, and F.F. Shih. 2008. Increased number and function of Foxp3 regulatory T cells during experimental arthritis. Arthritis and Rheumatism 58 (12): 3730–3741.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Belkaid, Y. 2007. Regulatory T cells and infection: a dangerous necessity. Nature Reviews Immunology 7 (11): 875–888.

    Article  PubMed  CAS  Google Scholar 

  18. Flores-García, Y., J.L. Rosales-Encina, V.H. Rosales-García, A.R. Satoskar, and P. Talamás-Rohana. 2013. Cd4+ cd25+ Foxp3+ Treg cells induced by rSSP4 derived from T. cruzi amastigotes increase parasitemia in an experimental Chagas disease model. BioMed Research International 2013 (1): 632436.

    PubMed  Google Scholar 

  19. Manuscript, A., G. Schett, J.M. Dayer, B. Manger, F.A. Amaral, V.V. Costa, et al. 2015. Mechanisms of inflammation in gout. Rheumatology 12 (2): 1090–1096.

    Google Scholar 

  20. Martinon, F., V. Pétrilli, A. Mayor, A. Tardivel, and J. Tschopp. 2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440 (7081): 237–241.

    Article  PubMed  CAS  Google Scholar 

  21. Acosta-Rodriguez, E.V., G. Napolitani, A. Lanzavecchia, and F. Sallusto. 2007. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nature Immunology 8 (9): 942–949.

    Article  PubMed  CAS  Google Scholar 

  22. Feldhoff, L.M., C.M. Rueda, M.E. Moreno-Fernandez, J. Sauer, C.M. Jackson, C.A. Chougnet, et al. 2017. IL-1beta induced HIF-1alpha inhibits the differentiation of human FOXP3(+) T cells. Scientific Reports 7: 465.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Kimura, A., and T. Kishimoto. 2010. IL-6: regulator of Treg/Th17 balance. European Journal of Immunology 40 (7): 1830–1835.

    Article  PubMed  CAS  Google Scholar 

  24. Scanu, A., F. Oliviero, R. Ramonda, P. Frallonardo, J.M. Dayer, and L. Punzi. 2012. Cytokine levels in human synovial fluid during the different stages of acute gout: role of transforming growth factor β1 in the resolution phase. Annals of the Rheumatic Diseases 71 (4): 621–624.

    Article  PubMed  CAS  Google Scholar 

  25. Jamshidian, A., V. Shaygannejad, A. Pourazar, S.H. Zarkeshesfahani, and M. Gharagozloo. 2013. Biased Treg/Th17 balance away from regulatory toward inflammatory phenotype in relapsed multiple sclerosis and its correlation with severity of symptoms. Journal of Neuroimmunology 262 (1–2): 106–112.

    Article  PubMed  CAS  Google Scholar 

  26. Tu, Z., H. Xue, W. Chen, L. Cao, and W. Zhang. 2017. Changes of treg and Th17 cells as well as cytokines in children with acute bronchitis. Experimental & Therapeutic Medicine 14 (4): 3846–3850.

    Article  CAS  Google Scholar 

  27. Abeles, A.M. 2015. Hyperuricemia, gout, and cardiovascular disease: an update. Current Rheumatology Reports 17 (3): 1–5.

    Article  CAS  Google Scholar 

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81671601; 81771774).

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    Authors and Affiliations

    1. Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated to Anhui Medical University, No.17 LuJiang Road, Hefei, 230001, China

      Xiao-Juan Dai, Jin-Hui Tao, Xuan Fang, Yuan Xia, Xiao-Mei Li & Xiang-Pei Li

    2. Centre for Transplantation and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia

      Yi-Ping Wang

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    1. Xiao-Juan Dai
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    Contributions

    X-J.D., X-P.L., and J-H.T. conceived and designed the study. X-J.D. and X.F. performed the experiments. X-J.D. and X-P.L. analyzed the statistics and results. Y-P.W., X-M.L., and Y.X participated in the discussion. X-J.D wrote the paper. All authors have reviewed the manuscript.

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    Correspondence to Xiang-Pei Li.

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    All protocols and procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at Anhui Provincial Hospital.

    Conflict of Interest

    The authors declare that they have no conflicts of interest.

    Additional information

    Xiao-Juan Dai and Jin-Hui Tao contributed equally to this work.

    Xiao-Juan Dai and Jin-Hui Tao are co-first authors.

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    Dai, XJ., Tao, JH., Fang, X. et al. Changes of Treg/Th17 Ratio in Spleen of Acute Gouty Arthritis Rat Induced by MSU Crystals. Inflammation 41, 1955–1964 (2018). https://doi.org/10.1007/s10753-018-0839-y

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    • DOI: https://doi.org/10.1007/s10753-018-0839-y

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