[1]郑应麟 周希 杨治芳.SOCS1对CD4+T细胞分化的影响及其 在桥本甲状腺炎中的作用[J].国际内分泌代谢杂志,2018,38(05):293-297.[doi:10.3760/cma.j.issn.1673-4157.2018.05.002]
　Zheng Yinglin,Zhou Xi,Yang Zhifang.Effects of SOCS1 on CD4+T cell differentiation and its role in Hashimoto's thyroiditis[J].International Journal of Endocrinology and Metabolism,2018,38(05):293-297.[doi:10.3760/cma.j.issn.1673-4157.2018.05.002]
点击复制

SOCS1对CD4+T细胞分化的影响及其 在桥本甲状腺炎中的作用()
分享到：

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
38
期数:
2018年05期
页码:
293-297
栏目:
论著
出版日期:
2018-09-20

文章信息/Info

Title:
Effects of SOCS1 on CD4+T cell differentiation and its role in Hashimoto's thyroiditis
作者:
郑应麟 周希 杨治芳
作者单位:330006 南昌大学第一附属医院内分泌科
Author(s):
Zheng Yinglin;  Zhou Xi;  Yang Zhifang
Department of Endocrinology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
关键词:
桥本甲状腺炎;  细胞因子信号抑制因子1;  信号转导与转录激活因子3;  T细胞分化
Keywords:
Hashimoto's thyroiditis;  Cytokine signaling inhibitor 1;  Signal transduction and activator of transcription 3;  T cell differentiation
DOI:
10.3760/cma.j.issn.1673-4157.2018.05.002
摘要:
目的 探讨细胞因子信号抑制因子(SOCS)1对桥本甲状腺炎CD4+T细胞分化的影响。方法 从桥本甲状腺炎(HT)患者中分离CD4+T淋巴细胞和B淋巴细胞,分为pEF-FLAG-1空载体对照组、SOCS1转染组、信号转导与转录激活因子3(STAT3)沉默组、SOCS1转染+STAT3沉默组。在CD4+T细胞中采用基因转染技术上调SOCS1的表达,沉默STAT3基因,流式细胞术检测辅助性T细胞17(Th17)、调节性T细胞(Treg)和滤泡辅助性T细胞(Tfh)。荧光定量PCR检测CD4+T细胞视黄酸相关的孤儿受体(ROR)γt mRNA、转录因子叉头蛋白3(FoxP3)mRNA、B细胞淋巴瘤分子6(Bcl6)mRNA。ELISA检测白细胞介素(IL)-6、IL-17、IL-23、IL-21、转化生长因子(TGF)β1的水平。Western印迹法检测SOCS1和STAT3的蛋白水平。结果 SOCS1转染CD4+T细胞后,抑制Th17和Tfh(t=8.63、7.66,P均<0.01)。SOCS1抑制RORγt mRNA和Bcl6 mRNA,同时促进FoxP3 mRNA的表达(t=14.38、8.86、9.46,P均<0.01)。与SOCS1转染组和pEF-FLAG-1空载体对照组相比,SOCS1转染+STAT3沉默组对IL-6、IL-17、IL-23、IL-21的抑制和对TGFβ1的促进更明显(t=8.64、11.02、9.76、12.18、14.08,P均<0.01)。SOCS1转染组STAT3蛋白水平下降(t=5.12,P<0.05),SOCS1转染+STAT3沉默组STAT3蛋白水平显著低于pEF-FLAG-1空载体对照组(t=4.78,P<0.05)。结论 SOCS1通过抑制STAT3调控T细胞的分化,可能与HT的发病机制有关。
Abstract:
Objective To investigate the effect of cytokine signaling inhibitor(SOCS)1 on T cell differentiation in Hashimoto's thyroiditis(HT).Methods CD4+T lymphocytes and B lymphocytes were isolated from HT patients and divided into pEF-FLAG-1 empty vector control group, SOCS1 vector group, signal transduction and activator of transcription 3(STAT3)gene silencing group, and SOCS1 vector+STAT3 gene silencing group. The level of SOCS1 expression in CD4+T cells was up-regulated by gene transfection technique; STAT3 was silenced; T helper cell 17(TH17), regulatory cells(Treg)and follicular helper T cells(Tfh)were detected by flow cytometry. Fluorescent quantitative PCR was used to detect the mRNA level of retinoic acid-related orphan receptor γt(RORγt), forkhead box protein 3(FoxP3)and B cell lymphoma 6(Bcl6)in CD4+T cells. ELISA was used to detect the levels of interleukin-6(IL-6), interleukin-17(IL-17), interleukin-23(IL-23), interleukin-21(IL-21)and transforming growth factor β1(TGFβ1). Western blotting was used to detect the levels of SOCS1 and STAT3 protein.Results After transfection of CD4+T cells with SOCS1, TH17 and Tfh were inhibited(t=8.63, 7.66, all P<0.01). SOCS1 inhibited the expression of RORγt mRNA and Bcl6 mRNA, while promoted the expression of FoxP3 mRNA(t=14.38, 8.86,9.46,all P<0.01). Compared with SOCS1 vector group and pEF-FLAG-1 empty vector control group, the suppression of IL-6, IL-17, IL-23, IL-21 and the promotion of TGFβ1 were greater in SOCS1 vector + STAT3 silencing group(t=8.64, 11.02, 9.76, 12.18, 14.08, all P<0.01). The level of STAT3 protein was decreased in SOCS1 group(t=5.12, P<0.05), and the STAT3 protein level in SOCS1 vector + STAT3 silencing group was significantly down-regulated compared with that in pEF-FLAG-1 empty vector control group(t=4.78, P<0.05).Conclusion SOCS1 regulates T cell differentiation by inhibiting STAT3, which may be related to the pathogenesis of HT.

参考文献/References:


[1] Suciu-Foca N,Manavalan JS,Scotto L,et al.Molecular characterization of allospecific T suppressor and tolerogenic dendritic cells: review[J].Int Immunopharmacol,2005,5(1):7-11.DOI:10.1016/j.intimp.2004.09.003.
[2] Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation[J].Cell,2010,140(6):845-858.DOI:10.1016/j.cell.2010.02.021.
[3] Wang S,Baidoo SE,Liu Y,et al.T cell-derived leptin contributes to increased frequency of T helper type 17 cells in female patients with Hashimoto's thyroiditis[J].Clin Exp Immunol,2013,171(1):63-68.DOI:10.1111/j.1365-2249.2012.04670.x.
[4] Qin Q, Liu P, Liu L,et al. The increased but non-predominant expression of Th17- and Th1-specific cytokines in Hashimoto's thyroiditis but not in Graves' disease[J].Braz J Med Biol Res,2012,45(12):1202-1208.
[5] Mahony R,Ahmed S,Diskin C,et al.SOCS3 revisited: a broad regulator of disease, now ready for therapeutic use[J].Cell Mol Life Sci,2016,73(17):3323-3336.DOI:10.1007/s00018-016-2234-x.
[6] Morris GP,Brown NK,Kong YC.Naturally-existing CD4(+)CD25(+)Foxp3(+)regulatory T cells are required for tolerance to experimental autoimmune thyroiditis induced by either exogenous or endogenous autoantigen[J].J Autoimmun,2009,33(1):68-76.DOI:10.1016/j.jaut.2009.03.010.
[7] Korn T,Oukka M,Kuchroo V,et al.Th17 cells: effector T cells with inflammatory properties[J].Semin Immunol,2007,19(6):362-371.DOI:10.1016/j.smim.2007.10.007.
[8] Figueroa-Vega N,Alfonso-Pérez M,Benedicto I,et al.Increased circulating pro-inflammatory cytokines and Th17 lymphocytes in Hashimoto's thyroiditis[J].J Clin Endocrinol Metab,2010,95(2):953-962.DOI:10.1210/jc.2009-1719.
[9] Montagna G, Imperiali M, Agazzi P,et al. Hashimoto's encephalopathy: a rare proteiform disorder[J].Autoimmun Rev,2016,15(5):466-476.DOI:10.1016/j.autrev.2016.01.014.
[10] Bossowski A,Moniuszko M,D browska M,et al.Lower proportions of CD4+CD25(high)and CD4+FoxP3, but not CD4+CD25+CD127(low)FoxP3+ T cell levels in children with autoimmune thyroid diseases[J].Autoimmunity,2013,46(3):222-230.DOI:10.3109/08916934.2012.751981.
[11] Ramgolam VS, Markovic-Plese S. Regulation of suppressors of cytokinesignaling as a therapeutic approach in autoimmune diseases, with an emphasis on multiple sclerosis[J].J Signal Transduct,2011,2011:635721.DOI:10.1155/2011/635721.
[12] Palmer DC,Restifo NP.Suppressors of cytokine signaling(SOCS)in T cell differentiation, maturation, and function[J].Trends Immunol,2009,30(12):592-602.DOI:10.1016/j.it.2009.09.009.
[13] Jager LD,Dabelic R,Waiboci LW,et al.The kinase inhibitory region of SOCS-1 is sufficient to inhibit T-helper 17 and other immune functions in experimental allergic encephalomyelitis[J].J Neuroimmunol,2011,232(1-2):108-118. DOI:10.1016/j.jneuroim.2010.10.018.
[14] Zhu C,Ma J,Liu Y,et al.Increased frequency of follicular helper T cells in patients with autoimmune thyroid disease[J].J Clin Endocrinol Metab,2012,97(3):943-950.DOI:10.1210/jc.2011-2003.

相似文献/References:

[1]于亚静,杨彩哲,刘明,等.BRAFV600E在甲状腺乳头状癌与桥本甲状腺炎相关性中的研究[J].国际内分泌代谢杂志,2014,(06):375.[doi:10.3760/cma.j.issn.1673-4157.2014.06.004]
　Yu Yajing,Yang Caizhe,Liu ming,et al.Study of BRAFV600E in the correlation between papillary thyroid carcinoma and Hashimoto’s thyroiditis[J].International Journal of Endocrinology and Metabolism,2014,(05):375.[doi:10.3760/cma.j.issn.1673-4157.2014.06.004]
[2]贾媛媛,陈莉丽.Th17细胞与Graves病及桥本甲状腺炎[J].国际内分泌代谢杂志,2014,(05):344.[doi:10.3760/cma.j.issn.1673-4157.2014.05.016]
　Jia Yuanyuan,Chen Lili.Relationship between Th17 cells and Graves' disease,Hashimoto's thyroiditis[J].International Journal of Endocrinology and Metabolism,2014,(05):344.[doi:10.3760/cma.j.issn.1673-4157.2014.05.016]
[3]柴锦燕,方佩华,谭建,等.定量检测人甲状腺过氧化物酶抗体 化学发光酶免疫分析法的临床应用[J].国际内分泌代谢杂志,2016,36(01):24.[doi:10.3760/cma.j.issn.1673-4157.2016.01.006]
　Chai Jinyan,Fang Peihua,Tan Jian,et al.Clinical application of chemiluminescence enzyme immunoassay to quantitatively detect human thyroid peroxidase antibodies[J].International Journal of Endocrinology and Metabolism,2016,36(05):24.[doi:10.3760/cma.j.issn.1673-4157.2016.01.006]
[4]房方,卫红艳,王坤玲,等.硒治疗自身免疫性甲状腺疾病的荟萃分析[J].国际内分泌代谢杂志,2016,36(04):247.[doi:10.3760/cma.j.issn.1673-4157.2016.04.09]
　Fang Fang,Wei Hongyan,Wang Kunling,et al.A meta-analysis of selenium in the treatment of autoimmune thyroid diseases[J].International Journal of Endocrinology and Metabolism,2016,36(05):247.[doi:10.3760/cma.j.issn.1673-4157.2016.04.09]
[5]郑仁东,刘超.白细胞介素-6与甲状腺疾病[J].国际内分泌代谢杂志,2016,36(05):352.[doi:10.3760/cma.j.issn.1673-4157.2016.05.18]
　Zheng Rendong,Liu Chao.Interleukin-6 and thyroid disease[J].International Journal of Endocrinology and Metabolism,2016,36(05):352.[doi:10.3760/cma.j.issn.1673-4157.2016.05.18]
[6]郑慧娟,魏璠,魏军平.自噬与自身免疫性甲状腺疾病[J].国际内分泌代谢杂志,2017,37(01):17.[doi:10.3760/cma.j.issn.1673-4157.2017.01.05]
　Zheng Huijuan,Wei Fan,Wei Junping..Autophagy and autoimmune thyroid disease[J].International Journal of Endocrinology and Metabolism,2017,37(05):17.[doi:10.3760/cma.j.issn.1673-4157.2017.01.05]
[7]张玉洁 孟召伟 章明放 宋丽丽 李宁.甲状腺疾病的代谢组学研究现状[J].国际内分泌代谢杂志,2019,39(03):173.[doi:10.3760/cma.j.issn.1673-4157.2019.03.007]
　Zhang Yujie,Meng Zhaowei,Zhang Mingfang,et al.Research status of metabolomics in thyroid diseases[J].International Journal of Endocrinology and Metabolism,2019,39(05):173.[doi:10.3760/cma.j.issn.1673-4157.2019.03.007]

备注/Memo

备注/Memo:
作者单位:330006 南昌大学第一附属医院内分泌科
通信作者:杨治芳,Email:yzf1977728@hotmail.com
更新日期/Last Update: 2018-09-30