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Current Rheumatology Reviews

Author(s): Amany M. Tawfeik, Omnia A. El-dydamoni, Hend M. Maghraby, Eman Elshohat, Nora Seliem, Hanaa A. Abou elhassan, Eman A. Kassem and Haneya A. A. Anani*

DOI: 10.2174/1573397118666220401145710

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The Relationship Between FoxP3 and SOCs3 Gene Expressions and Disease Activity in Rheumatoid Arthritis

Page: [76 - 82] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: Immune dysregulation plays an important role in the pathogenesis of rheumatoid arthritis (RA). The CD4+CD25 high FoxP3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis. Negative regulation of JAK/STAT signaling is controlled by Suppressor of Cytokine Signaling (SOCs3) proteins. SOCs is produced at lower levels in RA. Our aim was to evaluate the expressional dysregulation of SOCs3 and FoxP3 genes in RA patients in relation to disease activity.

Methods: We have recruited 90 patients with RA and 60 healthy controls in case control study. Whole blood samples were collected from RA patients and healthy subjects. The measurement of FoxP3 and SOCs3 gene expression was performed by real-time PCR (qPCR).

Results: Patients with RA had significantly decreased expression levels of FoxP3 and SOCs3 genes in comparison with controls (P<0.001), in addition to the insignificance correlation of both genes with disease activity in RA patients.

Conclusion: FoxP3 and SOCs3 genes showed significant defects in rheumatoid arthritis patients with no significant difference in disease activity.

Keywords: 35366780

[1]
Raza K. The Michael Mason prize: Early rheumatoid arthritis-the window narrows. Rheumatology (Oxford) 2010; 49(3): 406-10.
[http://dx.doi.org/10.1093/rheumatology/kep392] [PMID: 19955223]
[2]
Firestein GS, McInnes IB. Immunopathogenesis of rheumatoid arthritis. Immunity 2017; 46(2): 183-96.
[http://dx.doi.org/10.1016/j.immuni.2017.02.006] [PMID: 28228278]
[3]
Tao JH, Cheng M, Tang JP, Liu Q, Pan F, Li XP. Foxp3, regulatory T cell, and autoimmune diseases. Inflammation 2017; 40(1): 328-39.
[http://dx.doi.org/10.1007/s10753-016-0470-8] [PMID: 27882473]
[4]
Byng-Maddick R, Ehrenstein MR. The impact of biological therapy on regulatory T cells in rheumatoid arthritis. Rheumatology (Oxford) 2015; 54(5): 768-75.
[http://dx.doi.org/10.1093/rheumatology/keu487] [PMID: 25667434]
[5]
Li B, Zheng SG. How regulatory T cells sense and adapt to inflammation. Cell Mol Immunol 2015; 12(5): 519-20.
[http://dx.doi.org/10.1038/cmi.2015.65] [PMID: 26277895]
[6]
Sun H, Gao W, Pan W, et al. Tim3+ Foxp3 + Treg cells are potent inhibitors of effector T cells and are suppressed in rheumatoid arthritis. Inflammation 2017; 40(4): 1342-50.
[http://dx.doi.org/10.1007/s10753-017-0577-6] [PMID: 28478516]
[7]
Rakesh K, Agrawal DK. Controlling cytokine signaling by constitutive inhibitors. Biochem Pharmacol 2005; 70(5): 649-57.
[http://dx.doi.org/10.1016/j.bcp.2005.04.042] [PMID: 15936728]
[8]
O’Shea JJ. Jaks, STATs, cytokine signal transduction, and immunoregulation: Are we there yet? Immunity 1997; 7(1): 1-11.
[http://dx.doi.org/10.1016/S1074-7613(00)80505-1] [PMID: 9252115]
[9]
Alexander WS. Suppressors of cytokine signalling (SOCS) in the immune system. Nat Rev Immunol 2002; 2(6): 410-6.
[http://dx.doi.org/10.1038/nri818] [PMID: 12093007]
[10]
Kubo M, Hanada T, Yoshimura A. Suppressors of cytokine signaling and immunity. Nat Immunol 2003; 4(12): 1169-76.
[http://dx.doi.org/10.1038/ni1012] [PMID: 14639467]
[11]
Wong PK, Egan PJ, Croker BA, et al. SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. J Clin Invest 2006; 116(6): 1571-81.
[http://dx.doi.org/10.1172/JCI25660] [PMID: 16710471]
[12]
Veenbergen S, Bennink MB, Affandi AJ, et al. A pivotal role for antigen-presenting cells overexpressing SOCS3 in controlling invariant NKT cell responses during collagen-induced arthritis. Ann Rheum Dis 2011; 70(12): 2167-75.
[http://dx.doi.org/10.1136/ard.2011.154815] [PMID: 21873688]
[13]
van den Brand BT, Abdollahi-Roodsaz S, Vermeij EA, et al. Therapeutic efficacy of Tyro3, Axl, and Mer tyrosine kinase agonists in collagen-induced arthritis. Arthritis Rheum 2013; 65(3): 671-80.
[http://dx.doi.org/10.1002/art.37786] [PMID: 23203851]
[14]
Isoma P, Alana T, Isohanni P, et al. The expression of SOCS is altered in rheumatoid arthritis. Rheumatology (Oxford) 2007; 46(10): 1538-46.
[http://dx.doi.org/10.1093/rheumatology/kem198]
[15]
Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum 2010; 62(9): 2569-81.
[http://dx.doi.org/10.1002/art.27584] [PMID: 20872595]
[16]
Morgan ME, Sutmuller RP, Witteveen HJ, et al. CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis. Arthritis Rheum 2003; 48(5): 1452-60.
[http://dx.doi.org/10.1002/art.11063] [PMID: 12746920]
[17]
Luo Q, Deng Z, Xu C, et al. Elevated expression of immunoreceptor Tyrosine-Based Inhibitory Motif (TIGIT) on T lymphocytes is correlated with disease activity in rheumatoid arthritis. Med Sci Monit 2017; 23: 1232-41.
[http://dx.doi.org/10.12659/MSM.902454] [PMID: 28282368]
[18]
Gavin MA, Torgerson TR, Houston E, et al. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc Natl Acad Sci USA 2006; 103(17): 6659-64.
[http://dx.doi.org/10.1073/pnas.0509484103] [PMID: 16617117]
[19]
Allan SE, Alstad AN, Merindol N, et al. Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Mol Ther 2008; 16(1): 194-202.
[http://dx.doi.org/10.1038/sj.mt.6300341] [PMID: 17984976]
[20]
Su Q, Jing J, Li W, et al. Impaired Tip60-mediated Foxp3 acetylation attenuates regulatory T cell development in rheumatoid arthritis. J Immunol 2019; 100: 27-39.
[http://dx.doi.org/10.1016/j.jaut.2019.02.007] [PMID: 30954385]
[21]
van Amelsfort JM, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LS. CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: Differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum 2004; 50(9): 2775-85.
[http://dx.doi.org/10.1002/art.20499] [PMID: 15457445]
[22]
Sempere-Ortells JM, Pérez-García V, Marín-Alberca G, et al. Quantification and phenotype of regulatory T cells in rheumatoid arthritis according to disease activity score-28. Autoimmunity 2009; 42(8): 636-45.
[http://dx.doi.org/10.3109/08916930903061491] [PMID: 19886735]
[23]
Zafari P, Yari K, Mostafaei S, et al. Analysis of Helios gene expression and Foxp3 TSDR methylation in the newly diagnosed rheumatoid arthritis patients. Immunol Invest 2018; 47(6): 632-42.
[http://dx.doi.org/10.1080/08820139.2018.1480029] [PMID: 29851536]
[24]
Li H, Yang D, Tang Z. Bcl2 like protein-12 suppresses Foxp3+ regulatory T cells in patients with rheumatoid arthritis. Am J Transl Res 2019; 11(5): 3048-55.
[PMID: 31217874]
[25]
Hashemi V, Farrokhi AS, Tanomand A, et al. Polymorphism of Foxp3 gene affects the frequency of regulatory T cells and disease activity in patients with rheumatoid arthritis in Iranian population. Immunol Lett 2018; 204(204): 16-22.
[http://dx.doi.org/10.1016/j.imlet.2018.10.001] [PMID: 30292536]
[26]
Paradowska-Gorycka A, Jurkowska M, Felis-Giemza A, et al. Genetic polymorphisms of Foxp3 in patients with rheumatoid arthritis. J Rheumatol 2015; 42(2): 170-80.
[http://dx.doi.org/10.3899/jrheum.131381] [PMID: 25448791]
[27]
Xiao H, Wang S, Miao R, Kan W. TRAIL is associated with impaired regulation of CD4+CD25- T cells by regulatory T cells in patients with rheumatoid arthritis. J Clin Immunol 2011; 31(6): 1112-9.
[http://dx.doi.org/10.1007/s10875-011-9559-x] [PMID: 21732015]
[28]
Lawson CA, Brown AK, Bejarano V, et al. Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood. Rheumatology (Oxford) 2006; 45(10): 1210-7.
[http://dx.doi.org/10.1093/rheumatology/kel089] [PMID: 16571607]
[29]
Walter GJ, Fleskens V, Frederiksen KS, et al. Phenotypic, functional, and gene expression profiling of peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127(low) treg cells in patients with chronic rheumatoid arthritis. Arthritis Rheumatol 2016; 68(1): 103-16.
[http://dx.doi.org/10.1002/art.39408] [PMID: 26314565]
[30]
Nie H, Zheng Y, Li R, et al. Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis. Nat Med 2013; 19(3): 322-8.
[http://dx.doi.org/10.1038/nm.3085] [PMID: 23396208]
[31]
Ji L, Geng Y, Zhou W, Zhang Z. A study on relationship among apoptosis rates, number of peripheral T cell subtypes and disease activity in rheumatoid arthritis. Int J Rheum Dis 2016; 19(2): 167-71.
[http://dx.doi.org/10.1111/1756-185X.12211] [PMID: 24618356]
[32]
Yang M, Liu Y, Mo B, et al. Helios but not CD226, TIGIT and Foxp3 is a potential marker for CD4+ treg cells in patients with rheumatoid arthritis. Cell Physiol Biochem 2019; 52: 1178-92.
[33]
Yamana J, Yamamura M, Okamoto A, et al. Resistance to IL-10 inhibition of interferon gamma production and expression of suppressor of cytokine signaling 1 in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res Ther 2004; 6(6): R567-77.
[http://dx.doi.org/10.1186/ar1445] [PMID: 15535835]
[34]
Shou J, Bull CM, Li L, et al. Identification of blood biomarkers of rheumatoid arthritis by transcript profiling of peripheral blood mono-nuclear cells from the rat collagen-induced arthritis model. Arthritis Res Ther 2006; 8(1): R28.
[http://dx.doi.org/10.1186/ar1883] [PMID: 16507131]