MiR-346 regulates CD4+CXCR5+ T cells in the pathogenesis of Graves’ disease
- 479 Downloads
Follicular helper T (Tfh) cells are increasingly recognized as participants in various autoimmune diseases, including Graves’ disease. Although many transcription factors and cytokines are known to regulate Tfh cells, the role of noncoding RNA in Tfh cells development and function is poorly understood. Twenty-three patients with GD, eleven patients with remitting GD, and twenty-four healthy controls were enrolled in the current study. The interaction of miRNA and target gene was predicted through software analysis and then validated by luciferase assay and Western blot. The levels of miR-346 in circulating CD4+ T cells and plasma were measured by qRT-PCR. The correlation of miR-346 levels with the percentages of CD4+CXCR5+T cells and autoantibody levels were also analyzed. Up-regulation of Bcl-6 and down-regulation of miR-346 in GD patients were observed, and miR-346 could inhibit Bcl-6 at both transcriptional and translational levels. Overexpression of miR-346 led to attenuating CD4+CXCR5+ T cells. The abnormal expression of miR-346 restored in GD patients after treatment. A negative correlation between levels of miR-346 and percentages of CD4+CXCR5+ T cells was confirmed in GD patients. Additionally, negative correlations between the levels of miR-346 in circulating CD4+ T cells and serum concentrations of TR-Ab, TG-Ab, and TPO-Ab were also revealed in GD patients. MiR-346 regulates CD4+CXCR5+ T cells by targeting Bcl-6, a positive regulator of Tfh cells, and might play an important role in the pathogenesis of Graves’ disease.
KeywordsMicroRNA-346 CD4+CXCR5+ T cells Bcl-6 Graves’ disease
This work was supported by the Specialized Research Fund for the Doctoral Program of Higher Education (Grant No. 20133227110008), National Natural Science Foundation of China (Grant Nos. 31100648, 81072453), Specialized Project for Clinical Medicine of Jiangsu Province (Grant No. BL2014065), Health Department Foundation of Jiangsu Province (Grant No. Z201312), Science and technology support program (Social Development) of Zhenjiang (Grant Nos. SH2013040, SH2014039) Graduate Student Research and Innovation Program of Jiangsu Province (Grant Nos. CXZZ13_0700, KYLX_1074), Jiangsu Province “333” Project, and Priority Academic Program Development of Jiangsu Higher Education Institutions.
Conflict of interest
The authors have no financial conflict of interest.
- 2.J. Rolf, S.E. Bell, D. Kovesdi, M.L. Janas, D.R. Soond, L.M. Webb, S. Santinelli, T. Saunders, B. Hebeis, N. Killeen, K. Okkenhaug, M. Turner, Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction. J. Immunol. 185(7), 4042–4052 (2010)PubMedCrossRefGoogle Scholar
- 7.D. Yu, S. Rao, L.M. Tsai, S.K. Lee, Y. He, E.L. Sutcliffe, M. Srivastava, M. Linterman, L. Zheng, N. Simpson, J.I. Ellyard, I.A. Parish, C.S. Ma, Q.J. Li, C.R. Parish, C.R. Mackay, C.G. Vinuesa, The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31(3), 457–468 (2009)PubMedCrossRefGoogle Scholar
- 15.S. Wang, S.E. Baidoo, Y. Liu, C. Zhu, J. Tian, J. Ma, J. Tong, J. Chen, X. Tang, H. Xu, L. Lu, T cell-derived leptin contributes to increased frequency of T helper type 17 cells in female patients with Hashimoto’s thyroiditis. Clin. Exp. Immunol. 171(1), 63–68 (2013)PubMedCentralPubMedCrossRefGoogle Scholar
- 24.X. Tang, X. Tian, Y. Zhang, W. Wu, J. Tian, K. Rui, J. Tong, L. Lu, H. Xu, S. Wang, Correlation between the frequency of Th17 cell and the expression of MicroRNA-206 in patients with dermatomyositis. Clin. Dev. Immunol. 2013, 7 (2013)Google Scholar
- 25.T. Thum, C. Gross, J. Fiedler, T. Fischer, S. Kissler, M. Bussen, P. Galuppo, S. Just, W. Rottbauer, S. Frantz, M. Castoldi, J. Soutschek, V. Koteliansky, A. Rosenwald, M.A. Basson, J.D. Licht, J.T. Pena, S.H. Rouhanifard, M.U. Muckenthaler, T. Tuschl, G.R. Martin, J. Bauersachs, S. Engelhardt, MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456(7224), 980–984 (2008)PubMedCrossRefGoogle Scholar
- 27.E. Stagakis, G. Bertsias, P. Verginis, M. Nakou, M. Hatziapostolou, H. Kritikos, D. Iliopoulos, D.T. Boumpas, Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann. Rheum. Dis. 70(8), 1496–1506 (2011)PubMedCrossRefGoogle Scholar
- 34.E. Sonkoly, P. Janson, M.L. Majuri, T. Savinko, N. Fyhrquist, L. Eidsmo, N. Xu, F. Meisgen, T. Wei, M. Bradley, J. Stenvang, S. Kauppinen, H. Alenius, A. Lauerma, B. Homey, O. Winqvist, M. Stahle, A. Pivarcsi, MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4. J Allergy Clin Immunol. 126(3), 581–589 (2010). e581–520PubMedCrossRefGoogle Scholar
- 37.J. Lin, T. Lwin, J.J. Zhao, W. Tam, Y.S. Choi, L.C. Moscinski, W.S. Dalton, E.M. Sotomayor, K.L. Wright, J. Tao, Follicular dendritic cell-induced microRNA-mediated upregulation of PRDM1 and downregulation of BCL-6 in non-Hodgkin’s B-cell lymphomas. Leukemia 25(1), 145–152 (2011)PubMedCentralPubMedCrossRefGoogle Scholar