Sat, Nov 23, 2024
Volume 13, Issue 6 (Nov-Dec 2019)
mljgoums 2019, 13(6): 29-35 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Bazzazi H, Yazdani Y, Behnampour N, Hossein-Nataj H, Memarian A, Aghaei M. Frequency of Th9 Cells in Different Stages of Rheumatoid Arthritis. mljgoums 2019; 13 (6) :29-35
URL: http://mlj.goums.ac.ir/article-1-1139-en.html
URL: http://mlj.goums.ac.ir/article-1-1139-en.html
Hadi Bazzazi1 
, Yaghoub Yazdani2 , Nasser Behnampour3 , Hadi Hossein-Nataj4 , Ali Memarian5 , Mehrdad Aghaei 6
, Yaghoub Yazdani2 , Nasser Behnampour3 , Hadi Hossein-Nataj4 , Ali Memarian5 , Mehrdad Aghaei 6
1- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran,
2- Infectious Diseases Research Center, Golestan University of Medical Sciences
3- Public Health Department, Faculty of Health, Golestan University of Medical Sciences, Gorgan, Iran.
4- Department of Immunology, Mazandaran University of Medical Sciences, Sari, Iran.
5- Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran
6- Division of Rheumatology, Department of Internal Medicine. Head, Joint, Bone, Connective tissue, Rheumatology Research Center (JBCRC)Deputy, Research & Development, Sayyad Shirazi Teaching Hospital Golestan University of Medical Sciences, Gorgan, Iran. ,mehrdadaghaie@yahoo.com
2- Infectious Diseases Research Center, Golestan University of Medical Sciences
3- Public Health Department, Faculty of Health, Golestan University of Medical Sciences, Gorgan, Iran.
4- Department of Immunology, Mazandaran University of Medical Sciences, Sari, Iran.
5- Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran
6- Division of Rheumatology, Department of Internal Medicine. Head, Joint, Bone, Connective tissue, Rheumatology Research Center (JBCRC)Deputy, Research & Development, Sayyad Shirazi Teaching Hospital Golestan University of Medical Sciences, Gorgan, Iran. ,
Abstract: (4371 Views)
ABSTRACT
Background and Objectives: T helper (Th) lymphocytes play a key role in the pathogenesis of autoimmune diseases. As a new subset of lymphocytes, Th9 is thought to be involved in a wide range of disorders including rheumatoid arthritis (RA). In this study, we evaluated frequency of Th9 and Th2 cells and its correlation with disease activity in patients with different stages of RA.
Methods: The frequency of circulating interleukin 9- and/or interleukin 4-producing CD3+CD8-T cells was determined among 41 patients with established RA, 14 patients with very early RA (VERA) and 23 healthy controls by flow cytometry analysis. Then, correlation of cell frequencies with disease activity score 28 (DAS-28) was assessed. Serum levels of interleukin 6 and anti-citrullinated peptide antibodies were measured by enzyme-linked immunosorbent assay.
Results: Frequency of Th9 cells was significantly higher in RA patients compared to healthy controls (P=0.009). Moreover, mean percentage of circulating Th9 cells in patients with inactive VERA was significantly higher than that in those with active disease (P=0.046). In addition, mean percentage of Th9 cells had a negative correlation with the DAS-28 (r=-0.568, P<0.05). There was no significant correlation between the mean serum level of interleukin 6 and percentage of Th2 and Th9 cells (P>0.05).
Conclusion: Our results suggest that Th9 cells may have a potential role in RA initiation. Thus, targeting Th9 cells could be a promising strategy for advanced RA therapies.
Keywords: Rheumatoid arthritis, Th2 cells, Th9 cells.
Background and Objectives: T helper (Th) lymphocytes play a key role in the pathogenesis of autoimmune diseases. As a new subset of lymphocytes, Th9 is thought to be involved in a wide range of disorders including rheumatoid arthritis (RA). In this study, we evaluated frequency of Th9 and Th2 cells and its correlation with disease activity in patients with different stages of RA.
Methods: The frequency of circulating interleukin 9- and/or interleukin 4-producing CD3+CD8-T cells was determined among 41 patients with established RA, 14 patients with very early RA (VERA) and 23 healthy controls by flow cytometry analysis. Then, correlation of cell frequencies with disease activity score 28 (DAS-28) was assessed. Serum levels of interleukin 6 and anti-citrullinated peptide antibodies were measured by enzyme-linked immunosorbent assay.
Results: Frequency of Th9 cells was significantly higher in RA patients compared to healthy controls (P=0.009). Moreover, mean percentage of circulating Th9 cells in patients with inactive VERA was significantly higher than that in those with active disease (P=0.046). In addition, mean percentage of Th9 cells had a negative correlation with the DAS-28 (r=-0.568, P<0.05). There was no significant correlation between the mean serum level of interleukin 6 and percentage of Th2 and Th9 cells (P>0.05).
Conclusion: Our results suggest that Th9 cells may have a potential role in RA initiation. Thus, targeting Th9 cells could be a promising strategy for advanced RA therapies.
Keywords: Rheumatoid arthritis, Th2 cells, Th9 cells.
Research Article: Original Paper |
Subject:
Immunology
Received: 2018/11/14 | Accepted: 2018/11/20 | Published: 2019/12/10 | ePublished: 2019/12/10
Received: 2018/11/14 | Accepted: 2018/11/20 | Published: 2019/12/10 | ePublished: 2019/12/10
References
1. Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010; 376(9746): 1094-108. doi: 10.1016/S0140-6736(10)60826-4. [DOI:10.1016/S0140-6736(10)60826-4]
2. Uhlig T, Moe RH, Kvien TK. The burden of disease in rheumatoid arthritis. Pharmacoeconomics. 2014; 32(9): 841-851. doi: 10.1007/s40273-014-0174-6. [DOI:10.1007/s40273-014-0174-6]
3. Cope AP, Schulze-Koops H, Aringer M. The central role of T cells in rheumatoid arthritis. Clin Exp Rheumatol. 2007; 25(5 Suppl 46): S4-11.
4. Gizinski AM, Fox DA. T cell subsets and their role in the pathogenesis of rheumatic disease. Curr Opin Rheumatol. 2014; 26(2): 204-10. doi: 10.1097/BOR.0000000000000036. [DOI:10.1097/BOR.0000000000000036]
5. Li P, Spolski R, Liao W, Leonard WJ. Complex interactions of transcription factors in mediating cytokine biology in T cells. Immunol Rev. 2014; 261(1): 141-156. [DOI:10.1111/imr.12199]
6. Burkett PR, Lee Y, Peters A, Kuchroo VK. T Cells and their Subsets in Autoimmunity. In: Rose NR, Mackay IR, editors. The Autoimmune Diseases. USA: Academic Press. 2014; 69-86. [DOI:10.1016/B978-0-12-384929-8.00006-X]
7. Patel DD, Kuchroo VK. Th17 Cell Pathway in Human Immunity: Lessons from Genetics and Therapeutic Interventions. Immunity. 2015; 43 (6): 1040-1051. doi: 10.1016/j.immuni.2015.12.003. [DOI:10.1016/j.immuni.2015.12.003]
8. van Vollenhoven RF. Rheumatoid arthritis in 2012: Progress in RA genetics, pathology and therapy. Nat Rev Rheumatol. 2013; 9(2): 70-2. doi: 10.1038/nrrheum.2012.232. [DOI:10.1038/nrrheum.2012.232]
9. Pandya JM, Lundell AC, Hallström M, Andersson K, Nordström I, Rudin A. Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects. J Leukoc Biol. 2016; 100 (4): 823-833. [DOI:10.1189/jlb.5A0116-025R]
10. Kaplan MH, Hufford MM, Olson MR. The development and in vivo function of T helper 9 cells. Nat Rev Immunol. 2015; 15(5): 295-307. doi: 10.1038/nri3824. [DOI:10.1038/nri3824]
11. Végran F, Apetoh L, Ghiringhelli F. Th9 cells: a novel CD4 T-cell subset in the immune war against cancer. Cancer Res. 2015; 75(3): 475-479. [DOI:10.1158/0008-5472.CAN-14-2748]
12. Talotta R, Berzi A, Atzeni F, Dell'Acqua D, Sarzi Puttini P, Trabattoni D. Evaluation of Th9 lymphocytes in peripheral blood of rheumatoid arthritis patients and correlation with anti-tumor necrosis factor therapy: results from an in vitro pivotal study. Reumatismo. 2016; 68(2): 83-89. [DOI:10.4081/reumatismo.2016.875]
13. Wilhelm C, Turner JE, Van Snick J, Stockinger B. The many lives of IL-9: a question of survival? Nat Immunol. 2012; 13(7): 637-641. [DOI:10.1038/ni.2303]
14. Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, et al. Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol. 2008; 9(12): 1341-1346. [DOI:10.1038/ni.1659]
15. van der Helm-van Mil AH1, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther. 2005; 7(5): R949-958. [DOI:10.1186/ar1767]
16. Kourilovitch M, Galarza-Maldonado C, Ortiz-Prado E. Diagnosis and classification of rheumatoid arthritis. J Autoimmun. 2014; 48-49: 26-30. doi: 10.1016/j.jaut.2014.01.027. [DOI:10.1016/j.jaut.2014.01.027]
17. Gremese E, Salaffi F, Bosello SL, Ciapetti A, Bobbio-Pallavicini F, Caporali R, et al. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study. Ann Rheum Dis. 2013; 72(6): 858-62. doi: 10.1136/annrheumdis-2012-201456. [DOI:10.1136/annrheumdis-2012-201456]
18. van Riel PL, Renskers L. The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. Clin Exp Rheumatol. 2016; 34(5 Suppl 101): S40-S44.
19. Møller BK, Andresen BS, Christensen EI, Petersen CM. Surface membrane CD4 turnover in phorbol ester stimulated T-lymphocytes. Evidence of degradation and increased synthesis. FEBS Lett. 1990; 276 (1-2): 59-62. DOI:10.1016/0014-5793(90)80506-e. [DOI:10.1016/0014-5793(90)80506-E]
20. Chang HC, Sehra S, Goswami R, Yao W, Yu Q, Stritesky GL, et al. The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat Immunol. 2010; 11(6): 527-34. doi: 10.1038/ni.1867. [DOI:10.1038/ni.1867]
21. Ciccia F, Guggino G, Ferrante A, Cipriani P, Giacomelli R, Triolo G. Interleukin-9 and T helper type 9 cells in rheumatic diseases. Clin Exp Immunol. 2016; 185(2):125-32. doi: 10.1111/cei.12807. [DOI:10.1111/cei.12807]
22. Yao W, Zhang Y, Jabeen R, Nguyen ET, Wilkes DS, Tepper RS, et al. Interleukin-9 is required for allergic airway inflammation mediated by the cytokine TSLP. Immunity. 2013; 38 (2): 360-372. doi: 10.1016/j.immuni.2013.01.007. [DOI:10.1016/j.immuni.2013.01.007]
23. Li J, Chen S, Xiao X, Zhao Y, Ding W, Li XC. IL-9 and Th9 cells in health and diseases-From tolerance to immunopathology. Cytokine Growth Factor Rev. 2017; 37: 47-55. doi: 10.1016/j.cytogfr.2017.07.004. [DOI:10.1016/j.cytogfr.2017.07.004]
24. Schmitt E, Klein M, Bopp T. Th9 cells, new players in adaptive immunity. Trends Immunol. 2014; 35(2): 61-8. doi: 10.1016/j.it.2013.10.004. [DOI:10.1016/j.it.2013.10.004]
25. Jäger A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 2009; 183 (11): 7169-7177. [DOI:10.4049/jimmunol.0901906]
26. Chowdhury K, Kumar U, Das S, Chaudhuri J, Kumar P, Kanjilal M, et al. Synovial IL-9 facilitates neutrophil survival, function and differentiation of Th17 cells in rheumatoid arthritis. Arthritis Res Ther. 2018; 20(1): 18. doi: 10.1186/s13075-017-1505-8. [DOI:10.1186/s13075-017-1505-8]
27. Kundu-Raychaudhuri S, Abria C, Raychaudhuri SP. IL-9, a local growth factor for synovial T cells in inflammatory arthritis. Cytokine. 2016; 79: 45-51. doi: 10.1016/j.cyto.2015.12.020. [DOI:10.1016/j.cyto.2015.12.020]
28. Demoruelle MK, Deane KD. Treatment strategies in early rheumatoid arthritis and prevention of rheumatoid arthritis. Curr Rheumatol Rep. 2012; 14(5): 472-480. [DOI:10.1007/s11926-012-0275-1]
29. Ciccia F, Guggino G, Rizzo A, Manzo A, Vitolo B, La Manna MP, et al. Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2015; 54(12): 2264-72. doi: 10.1093/rheumatology/kev252. [DOI:10.1093/rheumatology/kev252]
30. Hughes-Austin JM, Deane KD, Derber LA, Kolfenbach JR, Zerbe GO, Sokolove J, et al. Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA). Ann Rheum Dis. 2013; 72 (6): 901-907. [DOI:10.1136/annrheumdis-2012-201505]
31. Ruocco G, Rossi S, Motta C, Macchiarulo G, Barbieri F, De Bardi M, et al. T helper 9 cells induced by plasmacytoid dendritic cells regulate interleukin-17 in multiple sclerosis. Clin Sci (Lond). 2015; 129(4): 291-303. [DOI:10.1042/CS20140608]
32. Pan HF, Leng RX, Li XP, Zheng SG, Ye DQ. Targeting T-helper 9 cells and interleukin-9 in autoimmune diseases. Cytokine Growth Factor Rev. 2013; 24 (6): 515-522. [DOI:10.1016/j.cytogfr.2013.09.001]
33. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015; 16(5): 448-457. [DOI:10.1038/ni.3153]
34. Beriou G1, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, et al. TGF-beta induces IL-9 production from human Th17 cells. J Immunol. 2010; 185(1): 46-54. [DOI:10.4049/jimmunol.1000356]
35. Chen J, Li J, Gao H, Wang C, Luo J, Lv Z. Comprehensive evaluation of different T-helper cell subsets differentiation and function in rheumatoid arthritis. J Biomed Biotechnol. 2012; 2012: e535361. [DOI:10.1155/2012/535361]
36. Koetz K, Bryl E, Spickschen K, O'Fallon WM, Goronzy JJ, Weyand CM. T cell homeostasis in patients with rheumatoid arthritis. Proc Natl Acad Sci USA. 2000; 97(16): 9203-9208. [DOI:10.1073/pnas.97.16.9203]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
Enamad
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.