Research on the Mechanism of T Cell Subsets and Cytokines in Hashimoto's Thyroiditis
As being one of the most common diseases in autoimmune thyroid disease (AITD), Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease. It is mostly related to genetics, infection, and excessive iodine, but the exact pathogenesis has not yet clear. As one of the most important immune cells, T cells play an important role in the human immune. Helper T cells (Th) and regulatory T cells (Treg) are two important subgroups of T cells. The former include Th1, Th2, Th17 and other cells. HT patients is mainly characterized by expressing Th1 cytokines. The imbalance of Th1/Th2 ratio can induce abnormal immune response, which is closely related to the incidence of HT. Th17/Treg cells are mutually restricted in differentiation and mutually antagonistic in function. IL-17 secreted by Th17 cells directly promotes the inflammatory response of thyroid tissue and accelerates the damage of thyroid tissue. Abnormal Treg cell function cannot effectively inhibit the occurrence of autoimmune reactions and promote immune tolerance. Th17/Treg constitute a relatively independent group of cell networks except Th1/Th2. Under normal circumstances, Th1/Th2 and Th17/Treg cells maintain a dynamic balance. However, once unbalanced, they will lead to immune dysfunction and participate in the development of HT. This article reviews the mechanisms of Th1/Th2 and Th17/Treg cells and their cytokines in the pathogenesis of HT.
Research on the Mechanism of T Cell Subsets and Cytokines in Hashimoto's Thyroiditis, American Journal of Biomedical and Life Sciences.
Vol. 8, No. 4,
2020, pp. 83-90.
Dumitru C, Kabat AM, Maloy KJ. Metabolic Adaptations of CD4+TCells in Inflammatory Disease [J]. Front Immunol, 2018, vol. 9, pp. 540.
Raphael I, Nalawade S, Eagar TN, et al. T cell subsets and their signature Cytokines inautoimmune and inflammatory disease [J]. Cytokine, 2015, vol. 74, pp. 5-17.
Khanolkar A, Williams MA, Harty JT. Antigen experience shapes phenotype and function of memory Th1 cells [J]. PLoS One, 2013, vol. 8, pp. e65234.
Sofian M, Aghakhani A, Farazi AA, et al. Serum profile of T helper 1 and T helper 2 cytokines in hepatitis C virus infected patients [J]. Hepat Mon, 2012, vol. 12, pp. e6156.
Esfahanian F, Naimi E, Doroodgar F, et al. Th1/Th2 cytokines in patients with Graves’disease with or without ophthalmopathy [J]. Iran J Allergy Asthma Immunol, 2013, vol. 12, pp. 168-175.
Hu S, Rayman MP. Multiple Nutritional Factors and the Risk of Hashimoto's Thyroiditis [J]. Thyroid. 2017, vol. 27, pp. 597-610.
Xie YS, Qin WW. Migration of Thl/Th2 cytokines in autoimmune thyroid disease Internal Medicine. 2009, vol. 4, pp. 295-297.
Ben-Skowronek I, Szewczyk L, Kulik-Rechberger B, et al. The differences in T and B cell subsets in thyroid of children with Graves' disease and Hashimoto's thyroiditis [J]. World J Pediatr. 2013, vol. 9, pp. 245-250.
Li LQ, Yang X, Feng J. Relationship Between Autoimmune Thyroid Disease and Cytokines of Th1/Th2. Medical Recapitulate, 2006, vol. 12, pp. 1160-1163.
Jiang L, Wang CJ. Th1/th2 cells and autoimmune thyroid disease Anhui Med J, 2012, vol. 33, pp. 5629-5631.
Nanba T. Watanabe M. Inoue N. et al. Increases of the Th1/Th2 cell ratio in severe Hashimoto's disease and in the proportion of Th17 cells in intractable Graves' disease [J]. Thyroid. 2009, vol. 19, pp. 495-501.
Lin L, Xiong F, Zhao XD, et al. Th1/Th2 cells polarization in children with autoimmune thyroid diseases. J Clin Pediatr, 2009, vol. 27, pp. 1111-1114.
Yang Y, Yang L, Xie LL, et al. Clinical significance of serum th1/th2 level in children with autoimmune thyroid disease Clin Focu, 2009, vol. 24, pp. 149-150.
Shen H, Hu L. The relationship between the imbalance of the Th1/Th2 cytokines and autoimmune thyroid disease. Chin J Prac Inter Med, 2009, vol. 29, pp. 253-253.
Kuang RJ, Sun LH. The role and clinical value of th1th2 cell imbalance in elderly patients with autoimmune thyroid disease China &Fore Med Treat, 2014, vol. 30, pp. 77-78.
Jiang YP, Zhang HL. Preliminary Study of Th1/Th2 Imbalance in Different Types of Autoimmune Thyroid Disease. J Med Res, 2014, vol. 43, pp. 111-112.
Wang Y, Kang ZQ, Zhang XF, et al. Changes and clinical significance of Th1/Th2cells and levels of plasma thyroid outoantibodies in patients with autoimmune thyroiditis. Prac J Clini Med, 2020, vol. 17, pp. 154-157.
Hou ZJ, Mu ZX, Wang CC. Research Progress of Th17/Treg Cells and Their Transcription Factors in Autoimmune Diseases [J]. American Journal of Clinical and Experimental Medicine, 2019, vol. 7, pp. 83-92.
Horie I, Abiru N, Sakamoto H, et al. Induction of autoimmune thyroiditis by depletion of CD4+CD25+regulatory T cells in thyroiditis-resistant IL-17, but not interferon-gamma receptor, knock out nonobese diabetic-H2h4 mice [J]. Endocrinology, 2011, vol. 152, pp. 4448-4454.
Li D, Cai W, Gu R, et al. Th17 cell plays a role in the pathogenesis of Hashimoto's thyroiditis in patients [J]. Clin Immunol, 2013, vol. 149, pp. 411-420.
Toussirot E. The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases [J]. Inflamm Allergy Drug Targets. 2012, vol. 11, pp. 159-168.
Shi Y, Wang H, Su Z, et al. Differentiation imbalance of Th1/Th17 in peripheral blood mononuclear cells might contribute to pathogenesis of Hashimoto's thyroiditis [J]. Scand J Immunol. 2010, vol. 72, pp. 250-255.
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, vol. 171, pp. 63-68.
Bossowski A, Moniuszko M, Idźkowska E, et al. Evaluation of CD4+CD161+CD196+ and CD4+IL-17+Th17 cells in the peripheral blood of young patients with Hashimoto's thyroiditis and Graves' disease [J]. Pediatr Endocrinol Diabetes Metab, 2012, vol. 18, pp. 89-95.
XieXY, Xi' er NY, GuoT, et al. TheAlterationoftheTh1, Th2, Th17, Treg Cells in the Peripheral Blood in Patients with Grave' sDisease (GD) and Hashimoto' s Thyroiditis with Hypothyroidism. J Radioimmunology, 2011, vol. 24, pp. 290-293.
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 [J]. 2012, vol. 45, pp. 1202-1208.
Konca Degertekin C, Aktas Yilmaz B, Balos Toruner F, et al. Circulating Th17 cytokine levels are altered in Hashimoto's thyroiditis [J]. Cytokine, 2016, vol. 80, pp. 13-17.
Chen WZ. Study on immune imbalance of Th17/Treg in patients with hashimoto's thyroiditis [D]. Master's degree thesis of nanchang university, 2012.
Esfahanian F, Ghelich R, Rashidian H, et al. Increased Levels of Serum Interleukin-17 in Patients with Hashimoto's Thyroiditis [J]. Indian J Endocrinol Metab, 2017, vol. 21, pp. 551-554.
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, vol. 95, pp. 953-962.
Korn T, Reddy J, Gao W, et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation [J]. Nat Med. 2007, vol. 13, pp. 423-431.
Yang X, Gao T, Shi R, et al. Effect of iodine excess on Th1, Th2, Th17, and Treg cell subpopulations in the thyroid of NOD. H-2h4 mice [J]. Biol Trace Elem Res. 2014, vol. 159, pp. 288-296.
Xue HB, Ma L, Li YB, et al. Correlation between Treg/Th17 cells imbalance and autoimmunity in Hashimoto thyroiditis Chin J Mode Med, 2012, vol. 22, pp. 67-71.
Chen ZJ, Liu C, Li Q, et al. The change of Th17 lymphocytes and cytokines in autoimmune thyroid diseases Immu J, 2011, vol. 27, pp. 785-788.
Zhao JH. Detection and significance of the alteration of Th17 cells in patients with Hashimoto's thyroiditis and Graves disease [D]. Jilin University Master's thesis, 2012.
Ruggeri RM, Saitta S, Cristani M, et al. Serum interleukin-23 (IL-23) is increased in Hashimoto' s thyroiditis [J]. Endocr J, 2014, vol. 61, pp. 359-363.
SunQK, Chen ZL, Li CH, et al. Investigation of theroles of interleukin 6 and transforming growth factor-β signaling in Thl7/Treg imbalance of Hashimotos thyroiditis. Chin J Endo Metab, 2015, vol. 31, pp. 320-326.
Cheng AR, Cheng Y, Sun BL. Regulatory T Cells and Its Mechanism of Immunosuppression [J]. Chin J Clin Neurosci, 2014, vol. 22, pp. 438-444.
Manolova I, Gerenova J, Ivanova M. Serum levels of transforming growth factor-β1 (TGF-β1) in patients with systemic lupus erythematosus and Hashimoto’s thyroiditis [J]. Eur Cytokine Netw, 2013, vol. 24, pp. 69-74.
Xue H, Wang W, Shan Z, et al. Dynamic changes of CD4+CD25+regulatory T cells in NOD. H-2h4 mice with iodine-induced autoimmune thyroiditis [J]. Biol Trace Elem Res. 2011, vol. 143, pp. 292-301.
Yoshimura A, Muto G. TGF-β function in immune suppression [J]. Curr Top Microbiol Immunol. 2011, vol. 350, pp. 127-47.
Roberto González-Amaro, Mónica Marazuela. T Regulatory (Treg) and T Helper 17 (Th17) Lymphocytes in Thyroid Autoimmunity. Endocrine, 2016, vol. 52, pp. 30-38.
Mao C, Wang S, Xiao Y, et al. Impairment of regulatory capacity of CD4+CD25+regulatory T cells mediated by dendritic cell polarization and hyperthyroidism in Graves' disease [J]. J Immunol. 2011, vol. 186, pp. 4734-4743.
Guo YY, Lu YL, Zhai HL, et al. Analysis of peripheral blood regulatory T cell count and clinical significance in patients with Hashimoto's thyroiditis. Clin Focu, 2011, vol. 26, pp. 62-64.
Gao ST, Zhu TN, Zhang YN, et al. The frequency and function of CD4+CD25+regulatory T cells in autoimmune thyroid diseases Chin J Immu, 2011, vol. 27, pp. 269-273.
Yang ZF, Wu F, Tang JZ, et al Study about the Regulatory T Cells in Patients with Hashimoto's Thyroiditis Chin Gene Prac, 2013, vol. 16, pp. 2477-2479.
Bi JH, Hao LX, Huang F, et al. Study on the clinical significance of detection of peripheral blood CD4+CD25+Foxp3+regulatory T cells and IL-10 in patients with Hashimoto thyroiditis. J Clin Exper Med, 2017, vol. 16, pp. 38-40.
Dou B. Significance of combined detection with CD4+CD25+regulatory T cells and complement C3, C4 levels for early diagnosis of HT and Graves disease. J Medical Forum 2019, vol. 40, pp. 24-27.
Fountoulakis S, Vartholomatos G, Kolaitis N, et al. HLADR expressing peripheral T regulatory cells in newly diagnosed patients with different forms of autoimmune thyroid disease [J]. Thyroid, 2008, vol. 18, pp. 1195-1200.
Marazuela M, García-López MA, Figueroa-Vega N, et al. Regulatory T cells in human autoimmune thyroid disease [J]. J Clin Endocrinol Metab. 2006, vol. 91, pp. 3639-3646.
Bao QY, Xu YS, Yang HY. Regulatory T Cells and Endocrine Diseases. Med Reca, 2014, vol. 20, pp. 3278-3280.
Glick AB, Wodzinski A, Fu P, et al. Impairment of regulatory T-cell function in autoimmune thyroid disease [J]. Thyroid, 2013, vol. 23, pp. 871-878.