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Aghajani, M., Rafiei, A., Ghaffari, J., Valadan, R., Kardan, M., Soltani, M., & Tahaghoghi, S. (2019). Immune Dysregulation in Children with Allergic Asthma: A Close Relationship Between IL-17 but not IL-4 or IFN-. Research in Molecular Medicine (RMM), 6(1), 16-29. https://doi.org/10.18502/rmm.v6i1.3926
https://doi.org/10.18502/rmm.v6i1.3926
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authors
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Meysam Aghajani
No author data available.
-
Alireza Rafiei
No author data available.
-
Javad Ghaffari
No author data available.
-
Reza Valadan
No author data available.
-
Mostafa Kardan
No author data available.
-
Mostafa Soltani
No author data available.
-
Sahar Tahaghoghi
No author data available.
Published Date
- Mar 11, 2019
Immune Dysregulation in Children with Allergic Asthma: A Close Relationship Between IL-17 but not IL-4 or IFN-
Abstract
Introduction: Allergic asthma is a chronic airway inflammatory disease often determined with degrees of inflammation, hypersensitivity, bronchial constriction, and airway changes. Th1, Th2, and Th17 cells are the main cells involved in asthma pathophysiology. To evaluate Th1, Th2, and Th17 functions by assessing INF-γ, IL-4, and IL-17 gene and protein levels in asthma patients and healthy controls.
Materials and Methods: In total, 44 individuals of Iranian ethnicity including 24 patients with allergic asthma and 20 healthy controls were enrolled. Peripheral blood mononuclear cells of all participants were isolated and cDNA was synthesized following RNA extraction. Gene expression and protein levels of INF-γ, IL-4, and IL-17 were evaluated by real-time polymerase chain reaction and sandwich ELISA, respectively.
Results: The results of this study showed that the gene expression of IL-4 and IL-17 in patients was increased significantly compared to the control group (p = 0.046 and 0.03, respectively) whereas that of IFN-γ was significantly decreased in the group of patients (p = 0.021). Compared to the healthy controls, serum levels of IL-17 and IL-4 were significantly increased in asthma patients (p = 0.015 and 0.03, respectively).
Conclusion: Higher IL-17 and IL-4 mRNA expression and serum levels in asthma patients than healthy controls highlight the role of Th2 and Th17 cells in asthma pathogenesis and their potential as therapeutic targets.
References
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[26] Wong CK, Ho CY, Ko FWS, Chan CHS, Ho ASS, Hui DSC, et al. Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-γ, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol. 2001;125(2):177–83.
[27] Gergen PJ, Mullally DI, Evans R, 3rd. National survey of prevalence of asthma among children in the United States, 1976 to 1980. Pediatrics. 1988;81(1):1–7. Epub 1988/01/01.
[28] Choudhry S, Seibold MA, Borrell LN, Tang H, Serebrisky D, Chapela R, et al. Dissecting complex diseases in complex populations: asthma in Latino Americans. Proc Am Thoracic Soc. 2007;4(3):226–33. Epub 20017/07/04.
[29] Glimcher SFL. 0T cell directives for transcriptional regulation in asthma. Springer Semin Immun. 20
[30] Xu D, Wang Y, Chen Z, Li S, Cheng Y, Zhang L, et al. Prevalence and risk factors for asthma among children aged 0–14 years in Hangzhou: a cross-sectional survey. Respir Res. 2016;17(1):122.
[31] Raghavan D, Jain R. Increasing awareness of sex differences in airway diseases. Respirology. 2016;21(3):449–59.
[32] Górska K, Paplińska-Goryca M, Nejman-Gryz P, Goryca K, Krenke R. Eosinophilic and neutrophilic airway inflammation in the phenotyping of mild-to-moderate asthma and chronic obstructive pulmonary disease. COPD. 2017;14(2):181–89.
[33] Bacharier LB, Jabara H, Geha RS. Molecular mechanisms of immunoglobulin E regulation. Int Arch Allergy Immunol. 1998;115(4):257–69.
[34] Barrett NA, Austen KF. Innate cells and T helper 2 cell immunity in airway inflammation. Immunity. 2009;31(3):425–37.
[35] Crimi E, Spanevello A, Neri M, Ind PW, Rossi GA, Brusasco V. Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med. 1998;157(1):4–9.
[36] Alizadeh-Navaei R, Rafiei A, Hedayatizadeh-Omran A, Mohammadzadeh I, Arabi M. Gene susceptibility in Iranian asthmatic patients: a narrative review. Ann Med Health Sci Res. 2014;4(6):837–40. doi: 10.4103/2141-9248.144871
[37] Chizzolini C, Chicheportiche R, Burger D, Dayer JM. Human Th1 cells preferentially induce interleukin (IL)-1beta while Th2 cells induce IL-1 receptor antagonist production upon cell/cell contact with monocytes. Eur J Immunol. 1997;27(1):171–77.
[38] Guerra ES, Lee CK, Specht CA, Yadav B, Huang H, Akalin A, et al. Central role of IL-23 and IL-17 producing eosinophils as immunomodulatory effector cells in acute pulmonary aspergillosis and allergic asthma. PLoS Pathog. 2017;13(1):e1006175
[39] Irvin C, Zafar I, Good J, Rollins D, Christianson C, Gorska MM, et al. Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma. J Allergy Clin Immunol. 2014;134(5):1175–86.
[2] Drazen JM. Asthma and the human genome project: summary of the 45th Annual Thomas L. Petty Aspen Lung Conference. Chest. 2003;123(3):447S-9S.
[3] BTS/SIGN. British guideline on the management of asthma. A national clinical guideline. 2008. British Thoracic Society and Scottish Intercollegiate Guidelines Network (SIGN). Available from: http://www.sign.ac.uk/guidelines/fulltext/ 101/index.html (Revised January 2012).
[4] Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004;170:836–44.
[5] Heydarnia A EA, Mehrabi Y, Porbak Z, Moien M. The prevalence of asthma symptoms in a country based on meta-analysis. J Beh Univ Med Sci. 2008;31:217–25.
[6] Zhu J, Yamane H, Cote-Sierra J, Guo L, Paul WE. GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res. 2006;16(1):3–10.
[7] Pober JS, Gimbrone MA Jr., Lapierre LA, Mendrick DL, Fiers W, Rothlein R et al. Overlapping patterns of activation of human endothelial cells by interleukin I, tumor necrosis factor, and immune interferon. J Immunol. 1986:137:1893–96.
[8] Romagnani S. Regulation and deregulation of human IgE synthesis. Immunol Today. 1990;11(9):316–21
[9] Wu W, Bleeckern E, Moore W, Busse W, Castro M, Chung KF et al. Unsupervised phenotyping of Severe Asthma Research Program participants using expanded lung data. J Allergy Clin Immunol. 2014;133(5):1280–88.
[10] Manni ML, Trudeau JB, Scheller EV, Mandalapu S, Elloso MM, Kolls JK, et al. The complex relationship between inflammation and lung function in severe asthma. Mucosal Immunol. 2014;7(5):1186–98.
[11] Sullivan SD, Rasouliyan L, Russo PA, Kamath T, Chipps BE. Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma. Allergy. 2007;62(2):126–33.
[12] Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012;18(5):673–83.
[13] Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, et al. T-helper type 2-driven inflammation defines major sub-phenotypes of asthma. Am J Respir Crit Care Med. 2009;180:388–95.
[14] De Boever EH, Ashman C, Cahn AP, Locantore NW, Overend P, Pouliquen IJ, et al. Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial. J Allergy Clin Immunol. 2014;133:989–96.
[15] Yao Z, Painter SL, Fanslow WC, Ulrich D, Macduff BM, Spriggs MK, et al. Human IL-17: a novel cytokine derived from T cells. J Immunol. 1995;155(12):5483–86.
[16] Fossiez F, Djossou O, Chomarat P, FloresRomo L, Ait-Yahia S, Maat C, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med. 1996;183(6):2593–603.
[17] Aggarwal S, Gurney AL. IL-17: prototype member of an emerging cytokine family. J Leukoc Biol. 2002;71(1):1–8.
[18] Al-Ramli W, Pr´efontaine D, Chouiali F, Martin JG, Olivenstein R, Lemi‘ere C, et al. T(H)17-associated cytokines (IL-17A and IL17F) in severe asthma. J Allergy Clin Immunol. 2009;123:1185—87
[19] Bullens DM, Truyen E, Coteur L, Dilissen E, Hellings PW, Dupont LJ, et al. IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res. 2006;7:135.
[20] Kudo M, Melton AC, Chen C, Engler MB, Huang KE, Ren X, et al. IL-17A produced by alpha beta T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med. 2012;18(4):547–54.
[21] Cao J, Ren G, Gong Y, Dong S, Yin Y, Zhang L. Bronchial epithelial cells release IL-6, CXCL1 and CXCL8 upon mast cell interaction. Cytokine. 2011;56:823–31.
[22] Ghaffari J, Rafiei AR, Ajami A, Mahdavi M, Hoshiar B. Serum interleukins 6 and 8 in mild and severe asthmatic patients, is it difference? Caspian J Intern Med. 2011;2(2):226–28.
[23] Kardan M, Ghaffari J, Valadan R, Rafiei A, Soltani M, Aghajani M et al . T-bet and
GATA-3 gene expression in children with allergic asthma and healthy controls. J Mazandaran Univ Med Sci. 2017;26(146):9–21.
[24] Kroegel C. Global Initiative for Asthma (GINA) guidelines: 15 years of application. Expert Rev Clin Immunol. 2009;5(3):239–49. doi: 10.1586/eci.09.1. PMID: 20477002
[25] Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-[Delta,Delta] CT method. Methods. 2001;25(4):402–08. doi: 10.1006/meth.2001.1262.
[26] Wong CK, Ho CY, Ko FWS, Chan CHS, Ho ASS, Hui DSC, et al. Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-γ, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol. 2001;125(2):177–83.
[27] Gergen PJ, Mullally DI, Evans R, 3rd. National survey of prevalence of asthma among children in the United States, 1976 to 1980. Pediatrics. 1988;81(1):1–7. Epub 1988/01/01.
[28] Choudhry S, Seibold MA, Borrell LN, Tang H, Serebrisky D, Chapela R, et al. Dissecting complex diseases in complex populations: asthma in Latino Americans. Proc Am Thoracic Soc. 2007;4(3):226–33. Epub 20017/07/04.
[29] Glimcher SFL. 0T cell directives for transcriptional regulation in asthma. Springer Semin Immun. 20
[30] Xu D, Wang Y, Chen Z, Li S, Cheng Y, Zhang L, et al. Prevalence and risk factors for asthma among children aged 0–14 years in Hangzhou: a cross-sectional survey. Respir Res. 2016;17(1):122.
[31] Raghavan D, Jain R. Increasing awareness of sex differences in airway diseases. Respirology. 2016;21(3):449–59.
[32] Górska K, Paplińska-Goryca M, Nejman-Gryz P, Goryca K, Krenke R. Eosinophilic and neutrophilic airway inflammation in the phenotyping of mild-to-moderate asthma and chronic obstructive pulmonary disease. COPD. 2017;14(2):181–89.
[33] Bacharier LB, Jabara H, Geha RS. Molecular mechanisms of immunoglobulin E regulation. Int Arch Allergy Immunol. 1998;115(4):257–69.
[34] Barrett NA, Austen KF. Innate cells and T helper 2 cell immunity in airway inflammation. Immunity. 2009;31(3):425–37.
[35] Crimi E, Spanevello A, Neri M, Ind PW, Rossi GA, Brusasco V. Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med. 1998;157(1):4–9.
[36] Alizadeh-Navaei R, Rafiei A, Hedayatizadeh-Omran A, Mohammadzadeh I, Arabi M. Gene susceptibility in Iranian asthmatic patients: a narrative review. Ann Med Health Sci Res. 2014;4(6):837–40. doi: 10.4103/2141-9248.144871
[37] Chizzolini C, Chicheportiche R, Burger D, Dayer JM. Human Th1 cells preferentially induce interleukin (IL)-1beta while Th2 cells induce IL-1 receptor antagonist production upon cell/cell contact with monocytes. Eur J Immunol. 1997;27(1):171–77.
[38] Guerra ES, Lee CK, Specht CA, Yadav B, Huang H, Akalin A, et al. Central role of IL-23 and IL-17 producing eosinophils as immunomodulatory effector cells in acute pulmonary aspergillosis and allergic asthma. PLoS Pathog. 2017;13(1):e1006175
[39] Irvin C, Zafar I, Good J, Rollins D, Christianson C, Gorska MM, et al. Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma. J Allergy Clin Immunol. 2014;134(5):1175–86.