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Correlation Between the Expression of MicroRNA-301a-3p and the Proportion of Th17 Cells in Patients with Rheumatoid Arthritis

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Abstract

Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and subsequent joint destruction. Previous studies have confirmed that Th17 cells play a critical role in the pathogenesis of RA. MicroRNA (miR)-301a-3p is a regulatory factor for Th17 cells differentiation that contributes to the pathogenesis of autoimmune diseases. The purposes of this study were to identify the alteration of Th17 cells and analyze the correlation between the expression of the miR-301a-3p and the proportion of Th17 cells in RA patients. The results showed that the frequency of Th17 cells and the expression of transcription factors (RORγt and STAT3) significantly increased in the peripheral blood mononuclear cells (PBMCs) from RA patients, and the associated proinflammatory cytokines were also upregulated. We also observed that the expression of protein inhibitor of activated STAT3 (PIAS3), the main cellular inhibitor of STAT3, was attenuated in RA patients and negatively correlated with the percentage of Th17 cells in RA. Interestingly, miR-301a-3p, an inhibitor of PIAS3 expression, was overexpressed in the PBMCs from RA patients and positively correlated with the frequency of Th17 cells in patients with RA. Taken together, these data indicated that miR-301a-3p and Th17 cells were augmented in peripheral blood, which may play an important role in the process of RA.

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References

  1. Abbas, A.K., K.M. Murphy, and A. Sher. 1996. Functional diversity of helper T lymphocytes. Nature 383: 787–793.

    Article  CAS  PubMed  Google Scholar 

  2. Annunziato, F., L. Cosmi, F. Liotta, E. Maggi, and S. Romagnani. 2013. Main features of human T helper 17 cells. The Annals of the New York Academy of Sciences 1283: 66–70.

    Article  Google Scholar 

  3. Harrington, L.E., R.D. Hatton, P.R. Mangan, H. Turner, T.L. Murphy, K.M. Murphy, et al. 2005. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature Immunology 6: 1123–1132.

    Article  CAS  PubMed  Google Scholar 

  4. Liang, S.C., X.Y. Tan, D.P. Luxenberg, R. Karim, K. Dunussi-Joannopoulos, M. Collins, et al. 2006. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. The Journal of Experimental Medicine 203: 2271–2279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Aujla, S.J., P.J. Dubin, and J.K. Kolls. 2007. Th17 cells and mucosal host defense. Seminars in Immunology 19: 377–382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bettelli, E., M. Oukka, and V.K. Kuchroo. 2007. Th-17 cells in the circle of immunity and autoimmunity. Nature Immunology 8: 345–350.

    Article  CAS  PubMed  Google Scholar 

  7. Seiderer, J., I. Elben, J. Diegelmann, J. Glas, J. Stallhofer, C. Tillack, et al. 2008. Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn’s disease and analysis of the IL17F p.His161Arg polymorphism in IBD. Inflammatory Bowel Diseases 14: 437–445.

    Article  PubMed  Google Scholar 

  8. Tang, X., X. Tian, Y. Zhang, W. Wu, J. Tian, K. Rui, et al. 2013. Correlation between the frequency of Th17 cell and the expression of microRNA-206 in patients with dermatomyositis. Clinical and Developmental Immunology 2013: 345347.

    PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  10. Volpe, E., N. Servant, R. Zollinger, S.I. Bogiatzi, P. Hupé, E. Barillot, and V. Soumelis. 2008. A critical function for transforming growth factor-beta, interleukin-23 and proinflammatory cytokines in driving and modulating human TH-17 responses. Nature Immunology 9: 650–657.

    Article  CAS  PubMed  Google Scholar 

  11. Ivanov, I.I., B.S. McKenzie, L. Zhou, C.E. Tadokoro, A. Lepelley, J.J. Lafaille, et al. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121–1133.

    Article  CAS  PubMed  Google Scholar 

  12. Mathur, A.N., H.C. Chang, D.G. Zisoulis, G.L. Stritesky, Q. Yu, J.T. O’Malley, et al. 2007. Stat3 and Stat4 direct development of IL-17-secreting Th cells. The Journal of Immunology 178: 4901–4907.

    Article  CAS  PubMed  Google Scholar 

  13. Yang, X.O., A.D. Panopoulos, R. Nurieva, S.H. Chang, D. Wang, S.S. Watowich, et al. 2007. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. The Journal of Biological Chemistry 282: 9358–9363.

    Article  CAS  PubMed  Google Scholar 

  14. Bixler, S.L., N.G. Sandler, D.C. Douek, and J.J. Mattapallil. 2013. Suppressed Th17 levels correlate with elevated PIAS3, SHP2, and SOCS3 expression in CD4 T cells during acute simian immunodeficiency virus infection. Journal of Virology 87: 7093–7101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Firestein, G.S. 2003. Evolving concepts of rheumatoid arthritis. Nature 423: 356–361.

    Article  CAS  PubMed  Google Scholar 

  16. van den Berg, W.B., and P. Miossec. 2009. IL-17 as a future therapeutic target for rheumatoid arthritis. Nature Reviews. Rheumatology 5: 549–553.

    Article  PubMed  Google Scholar 

  17. Cascão, R., R.A. Moura, I. Perpétuo, H. Canhão, E. Vieira-Sousa, A.F. Mourão, et al. 2010. Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis. Arthritis Research and Therapy 12: 196–204.

    Article  Google Scholar 

  18. Wang, S., Y. Shi, M. Yang, J. Ma, J. Tian, J. Chen, et al. 2012. GITRL exacerbates collagen-induced arthritis via enhancing the expansion of Th17 cells. The American Journal of Pathology 180: 1059–1067.

    Article  CAS  PubMed  Google Scholar 

  19. Stefani, G., and F.J. Slack. 2008. Small non-coding RNAs in animal development. Nature Reviews Molecular Cell Biology 9: 219–230.

    Article  CAS  PubMed  Google Scholar 

  20. Carlsen, A.L., A.J. Schetter, C.T. Nielsen, C. Lood, S. Knudsen, A. Voss, et al. 2013. Circulating microRNA expression profiles associated with systemic lupus erythematosus. Arthritis and Rheumatism 65: 1324–1334.

    Article  CAS  PubMed  Google Scholar 

  21. Chen, J., J. Tian, X. Tang, K. Rui, J. Ma, C. Mao, et al. 2015. MiR-346 regulates CD4(+)CXCR5 (+) T cells in the pathogenesis of Graves’ disease. Endocrine 49: 752–760.

    Article  CAS  PubMed  Google Scholar 

  22. Tian, J., K. Rui, X. Tang, J. Ma, Y. Wang, X. Tian, et al. 2015. MicroRNA-9 regulates the differentiation and function of myeloid-derived suppressor cells via targeting Runx1. The Journal of Immunology 195: 1301–1311.

    Article  CAS  PubMed  Google Scholar 

  23. Mycko, M.P., M. Cichalewska, A. Machlanska, H. Cwiklinska, M. Mariasiewicz, and K.W. Selmaj. 2012. MicroRNA-301a regulation of a T-helper 17 immune response controls autoimmune demyelination. Proceedings of the National Academy of Sciences of the United States of America 109: 1248–1257.

    Article  Google Scholar 

  24. Peng, H., Y. Liu, J. Tian, J. Ma, X. Tang, J. Yang, et al. 2015. Decreased expression of microRNA-125a-3p upregulates interleukin-23 receptor in patients with Hashimoto’s thyroiditis. Immunologic Research 62: 129–136.

    Article  CAS  PubMed  Google Scholar 

  25. Wang, Y., J. Tian, and S. Wang. 2015. The potential therapeutic role of myeloid-derived suppressor cells in autoimmune arthritis. Seminars in Arthritis and Rheumatism. doi:10.1016/j.semarthrit.2015.07.003.

    Google Scholar 

  26. Farid, S.Sh., G. Azizi, and A. Mirshafiey. 2013. Anti-citrullinated protein antibodies and their clinical utility in rheumatoid arthritis. International Journal of Rheumatic Diseases 16: 379–386.

    Article  CAS  PubMed  Google Scholar 

  27. Yang, D.H., C.C. Tu, S.C. Wang, C.C. Wei, and Y.W. Cheng. 2013. Circulating anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis and chronic obstructive pulmonary disease. Rheumatology International 34: 971–977.

    Article  PubMed  Google Scholar 

  28. Suzuki, M., M. Hashizume, H. Yoshida, and M. Mihara. 2010. Anti-inflammatory mechanism of tocilizumab, a humanized anti-IL-6R antibody: effect on the expression of chemokine and adhesion molecule. Rheumatology International 30: 309–315.

    Article  CAS  PubMed  Google Scholar 

  29. Darrieutort-Laffite, C., M.-A. Boutet, M. Chatelais, R. Brion, F. Blanchard, D. Heymann, et al. 2014. IL-1β and TNFα promote monocyte viability through the induction of GM-CSF expression by rheumatoid arthritis synovial Fibroblasts. Mediators of Inflammation 2014: 241840.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Aggarwal, S., N. Ghilardi, M.H. Xie, F.J. de Sauvage, and A.L. Gurney. 2003. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. The Journal of Biological Chemistry 278: 1910–1914.

    Article  CAS  PubMed  Google Scholar 

  31. Tang X, Tian J, Ma J, Wang J, Qi C, Rui K, et al. 2015. GITRL modulates the activities of p38 MAPK and STAT3 to promote Th17 cell differentiation in autoimmune arthritis. Oncotarget. doi:10.18632/oncotarget.6535.

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Acknowledgments

This work was financially supported through grants from the National Natural Science Foundation of China (grant no. 31170849, 31470881), Specialized Research Fund for the Doctoral Program of Higher School (grant no. 20133227110008), Health Department Foundation of Jiangsu Province (grant no. Z201312), Jiangsu Province “333” Project (grant no. BRA2015197), Summit of the Six Top Talents Program of Jiangsu Province (grant no. 2015-WSN-116), Jiangsu University Science Foundation (grant nos. 15JDG070, 11JDG093, FCJJ2015022), Jiangsu Key Laboratory of Laboratory Medicine Foundation (grant no. JSKLM-2014-010), and the Priority Academic Development Program of Jiangsu Higher Education Institutions.

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    Authors and Affiliations

    1. Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, 212002, China

      Xinyi Tang, Huaxi Xu & Shengjun Wang

    2. Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China

      Xinyi Tang, Jie Tian, Dong Shen, Lixian Yi, Ke Rui, Jie Ma & Shengjun Wang

    3. The Affiliated Hospital, Jiangsu University, Zhenjiang, 212001, China

      Kai Yin

    4. Department of Laboratory Medicine, Suzhou Municipal Hospital (Eastern), Suzhou, 215001, China

      Hongsheng Zhu

    5. Department of Laboratory Medicine, Suzhou Hospital Traditional Chinese Medicine, Suzhou, 215009, China

      Dong Shen

    6. Suzhou Health College, Suzhou, 215009, China

      Lixian Yi

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    1. Xinyi Tang
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    Xinyi Tang, Kai Yin and Hongsheng Zhu contributed equally to this work.

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    Tang, X., Yin, K., Zhu, H. et al. Correlation Between the Expression of MicroRNA-301a-3p and the Proportion of Th17 Cells in Patients with Rheumatoid Arthritis. Inflammation 39, 759–767 (2016). https://doi.org/10.1007/s10753-016-0304-8

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