Integrative Analysis of mRNA and miRNA Array Data Reveals the Suppression of Retinoic Acid Pathway in Regulatory T Cells of Graves' Disease
作者
Wang, Z;Fan, XH;Zhang, RR;Lin, ZW;Lu, T;Bai, X;Li, WC;Zhao, JJ;Zhang, QY
作者单位
[Wang, Zhe; Zhang, Rongrong; Lu, Ting; Li, Wenchao; Zhao, Jiajun] Shandong Univ, Shandong Prov Hosp, Div Endocrinol & Metab, Jinan 250021, Peoples R China.;-;[Fan, Xiaohua] Shandong Univ, Shandong Prov Hosp, Div Rehabil Med, Jinan 250021, Peoples R China.;-;[Bai, Xue] Shandong Univ, Natl Glycoengn Res Ctr, Jinan 250100, Peoples R China.;-;[Zhang, Qunye] Shandong Univ, Hosp 2, Cent Res Lab, Jinan 250033, Peoples R China.;-;[Lin, Zongwei; Zhang, Qunye] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ & Minist Publ Hlth, Qilu Hosp, Jinan 250100, Peoples R China.
摘要
Context: It is well known that regulatory T cells (Tregs) are abnormal in Graves' disease (GD) and play crucial roles in the breakdown of immune tolerance and GD development. However, there are controversies about whether the quantity and/or function of Tregs is aberrant in GD. The molecular mechanism of Tregs abnormality and its effects on GD development was still unclear, until now.;-;Objective: MiRNAs play important roles in the function and development of the immune system including Tregs. To reveal the Tregs abnormality and its molecular mechanism in GD, we systematically studied the quantity and immunosuppressive function as well as the differential expression profiles of miRNA and mRNA of Tregs in newly diagnosed patients with GD using TaqMan miRNA array and mRNA microarray.;-;Results: Our results showed that the quantity and immunosuppressive function of Tregs in initial patients with GD was significantly decreased. More importantly, the retinoic acid (RA) pathway was markedly suppressed and its agonist, all-trans retinoic acid, could notably improve the quantity and immunosuppressive function of Tregs from patients with GD in vitro. In addition, many other pathways including protein ubiquitination and circadian rhythm were also significantly regulated in Tregs of GD.;-;Conclusions: This integrative study first revealed the expression profiles of mRNA/miRNA in Tregs of initial GD and RA pathway might play important roles in GD development. Our results implied that all-trans RA, which had been used for a long time in the clinical setting, had potential value in the treatment of GD and was worthy of additional study.
关键词
AUTOIMMUNE THYROID-DISEASES; ACUTE PROMYELOCYTIC LEUKEMIA; FOXP3 EXPRESSION; DIFFERENTIATION; MICRORNAS; RECEPTOR; IMPAIRMENT; TOLERANCE; COLITIS; T(H)17
基本信息
