Volume 27, Issue 3 (Avicenna Journal of Clinical Medicine-Autumn 2020)                   Avicenna J Clin Med 2020, 27(3): 140-148 | Back to browse issues page


XML Persian Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Sheikh V, Hoseini Aghdam M, Behzad M. Evaluation of Percentage of Interferon-Gamma Secreting T Helper Cells and Expression of Related Genes in Patients with Type 2 Diabetes Mellitus. Avicenna J Clin Med 2020; 27 (3) :140-148
URL: http://sjh.umsha.ac.ir/article-1-2121-en.html
1- Assistant Professor, Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2- MSc in Immunology, Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
3- Associate Professor, Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran , mhd.behzad@yahoo.com
Abstract:   (2080 Views)
Background and Objective: The alterations of the adaptive immune system are involved in type 2 diabetes mellitus (T2DM) pathogenesis. T helper 1 (Th1) cells or CD4+ T cells are the pro-inflammatory components of adaptive immunity with the main feature of interferon-gamma (IFN-γ) secretion. The aim of this study was to evaluate the percentage of IFN-γ, assess the expression of related-genes in CD4+ T cells, including T-bet, IRF1, RUNX3, and NFκB, and determine the correlation between them and clinical parameters in T2DM patients.
Materials and Methods: In this case-control study, peripheral blood CD4+ T cells were isolated from 40 patients and 40 healthy controls (HCs). The percentage of IFN-γ secreting CD4+ T cells was assessed using flow cytometry, and the related-genes were evaluated using real-time polymerase chain reaction.
Results: The percentage of IFN-γ secreting CD4+ T cells significantly increased in the patients in comparison to that of the HCs (P<0.001). The expression levels of IRF1 and NFκB were higher in the patients in comparison to those of the HCs (P=0.02 and P<0.001, respectively). A significant positive correlation between IFN-γ secreting CD4+ T cells and both IRF1 and NFκB was observed in the patients (P=0.001 and P=0.002, respectively). There was a significant positive correlation between IFN-γ secreting CD4+ T cells, IRF1, and NFκB with fasting plasma glucose and hemoglobin A1c in the patients (P<0.001).
Conclusion: Due to the increased response of Th1 cells (the production of IFN-γ and expression of related genes) in the patients and existing correlation between them and plasma glucose level, it seems that these inflammatory factors are involved in T2DM pathogenesis, and the use of IFN-γ pathway antagonists could be considered a novel therapeutic approach.
 
Full-Text [PDF 1081 kb]   (810 Downloads)    
Type of Study: Original | Subject: Immunology

References
1. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98-107. PMID: 2123385 DOI: 10.1038/nri2925
2. Pawlak M, Ho AW, Kuchroo VK. Cytokines and transcription factors in the differentiation of CD4(+) T helper cell subsets and induction of tissue inflammation and autoimmunity. Curr Opin Immunol. 2020;67(2):57-67. PMID: 33039897 DOI: 10.1016/j.coi.2020.09.001
3. Christie D, Zhu J. Transcriptional regulatory networks for CD4 T cell differentiation. Curr Top Microbiol Immunol. 2014;381(1):125-72. PMID: 24839135 DOI: 10.1007/82_2014_372
4. Borzouei S, Sheikh V, Ghasemi M, Zamani A. Anti-inflammatory effect of combined sitagliptin and vitamin D3 on cytokines profile in patients with type 2 diabetes mellitus. J Interferon Cytokine Res. 2019;39(5):293-301. PMID: 30855208 DOI: 10.1089/jir.2018.0144
5. Zhang C, Xiao C, Wang P, Xu W. The alteration of Th1/Th2/Th17/Treg paradigm in patients with type 2 diabetes mellitus: relationship with diabetic nephropathy. Hum Immunol. 2014;75(4):289-96. PMID: 24530745 DOI: 10.1016/j.humimm.2014.02.007
6. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74(1):5-17. PMID: 25458968 DOI: 10.1016/j.cyto.2014.09.011
7. Fenimore J, Yaung HA. Regulation of IFN-γ expression. Adv Exp Med Biol. 2016;941(1):1-19. PMID: 27734406 DOI: 10.1007/978-94-024-0921-5_1
8. Djuretic IM, Levanon D, Negreanu V, Groner Y, Rao A, Ansel KM. Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat Immunol. 2007;8(2):145-53. PMID: 17195845 DOI: 10.1038/ni1424
9. Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MG, et al. Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis Rheum. 2004;50(12):3958-67. PMID: 15593221 DOI: 10.1002/art.20798
10. Negishi H, Taniguchi T, Yanai H. The interferon (IFN) class of cytokines and the IFN regulatory factor (IRF) transcription factor family. Cold Spring Harb Perspect Biol. 2018;10(11):258-78. PMID: 28963109 DOI: 10.1101/cshperspect.a028423
11. Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev. 2014;13(6):668-77. PMID: 24418308 DOI: 10.1016/j.autrev.2013.12.004
12. Qiao YC, Shen J, He L, Hong XZ, Tian F, Pan YH, et al. Changes of regulatory T cells and of proinflammatory and immunosuppressive cytokines in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. J Diabetes Res. 2016;36(9):49-57. PMID: 27777959 DOI: 10.1155/2016/3694957
13. Spranger J, Kroke A, Möhlig M, Hoffmann K, Bergmann MM, Ristow M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes. 2003;52(3):812-7. PMID: 12606524 DOI: 10.2337/diabetes.52.3.812
14. Jagannathan-Bogdan M, McDonnell ME, Shin H, Rehman Q, Hasturk H, Apovian CM, et al. Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes.J Immunol. 2011;186(2):1162-72. PMID: 12606524 DOI: 10.2337/diabetes.52.3.812
15. Telikani Z, Sheikh V, Zamani A, Borzouei S, Salehi I, Amirzargar MA, et al. Effects of sitagliptin and vitamin D3 on T helper cell transcription factors and cytokine production in clinical subgroups of type 2 diabetes mellitus: highlights upregulation of FOXP3 and IL-37. Immunopharmacol Immunotoxicol. 2019;41(2):299-311. PMID: 30907193 DOI: 10.1080/08923973.2019.1593447
16. Frisullo G, Angelucci F, Caggiula M, Nociti V, Iorio R, Patanella AK, et al. pSTAT1, pSTAT3, and T-bet expression in peripheral blood mononuclear cells from relapsing-remitting multiple sclerosis patients correlates with disease activity. J Neurosci Res. 2006;84(5):1027-36. PMID: 16865709 DOI: 10.1002/jnr.20995
17. Li Y, Ji X, Su Z, Tong J, Xia S, Chen X, et al. Downregulation of Runx3 is closely related to the decreased Th1-associated factors in patients with gastric carcinoma. Tumour Biol. 2014;35(12):12235-44. PMID: 25270738 DOI: 10.1007/s13277-014-2532-6
18. Liu M, Liu J, Hao S, Wu P, Zhang X, Xiao Y, et al. Higher activation of the interferon-gamma signaling pathway in systemic lupus erythematosus patients with a high type I IFN score: relation to disease activity. Clin Rheumatol. 2018;37(10):2675-84. PMID: 29774490 DOI: 10.1007/s10067-018-4138-7
19. Salvati VM, MacDonald TT, del Vecchio Blanco G, Mazzarella G, Monteleone I, Vavassori P, et al. Enhanced expression of interferon regulatory factor-1 in the mucosa of children with celiac disease. Pediatr Res. 2003;54(3):312-8. PMID: 12788988 DOI: 10.1203/01.PDR.0000079184.70237.9C
20. Hoseini-Aghdam M, Sheikh V, Eftekharian MM, Rezaeepoor M, Behzad M. Enhanced expression of TIGIT but not neuropilin-1 in patients with type 2 diabetes mellitus. Immunol Lett. 2020;225(1):1-8. PMID: 32540486 DOI: 10.1016/j.imlet.2020.06.003
21. Qiao J, Liu Y, Wu Y, Li X, Zhu F, Xia Y, et al. Aberrant expression of RUNX3 in patients with immune thrombocytopenia. Int Immunopharmacol. 2015;28(1):252-6. PMID: 26093269 DOI: 10.1016/j.intimp.2015.06.008
22. Song C, Hsu K, Yamen E, Yan W, Fock J, Witting PK, et al. Serum amyloid A induction of cytokines in monocytes/ macrophages and lymphocytes. Atherosclerosis. 2009; 207(2):374-83. PMID: 19535079 DOI: 10.1016/j.atherosclerosis.2009.05.007
23. O'Shea JJ, Ma A, Lipsky P. Cytokines and autoimmunity. Nat Rev Immunol. 2002;2(1):37-45. PMID: 11905836 DOI:10.1038/nri702
24. Navarro-González JF, Mora-Fernández C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol. 2008;19(3):433-42. PMID: 18256353 DOI: 10.1681/ASN.2007091048
25. Gutcher I, Becher B. APC-derived cytokines and T cell polarization in autoimmune inflammation. J Clin Invest. 2007;117(5):1119-27. PMID: 17476341 DOI: 10.1172/JCI31720

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Avicenna Journal of Clinical Medicine

Designed & Developed by : Yektaweb