Th1, Th2, and Th17 cytokines in systemic lupus erythematosus

References

• Gaber W, Sayed S, Rady HM, et al. Interleukin-27 and its relation to disease parameters in SLE patients. Egypt Rheumatol. 2012;34(3):99–105.
   Google Scholar
• Trouw LA, Pickering MC, Blom AM. The complement system as a potential therapeutic target in rheumatic disease. Nat Rev Rheumatol. 2017;13(9):538–547.
   PubMed Web of Science ®Google Scholar
• Fu SM, Dai C, Zhao Z, et al. Anti-dsDNA Antibodies are one of the many autoantibodies in systemic lupus erythematosus. F1000Res. 2015;4:939.
   PubMedGoogle Scholar
• Pisetsky DS. Anti-DNA antibodies–quintessential biomarkers of SLE. Nat Rev Rheumatol. 2016;12(2):102–110.
   PubMed Web of Science ®Google Scholar
• Qi S, Chen Q, Xu D, et al. Clinical application of protein biomarkers in lupus erythematosus and lupus nephritis. Lupus. 2018;27(10):1582–1590.
   PubMed Web of Science ®Google Scholar
• Tenbrock K, Juang YT, Kyttaris VC, et al. Altered signal transduction in SLE T cells. Rheumatology (Oxford). 2007;46(10):1525–1530.
   PubMed Web of Science ®Google Scholar
• Sanz I. Rationale for B cell targeting in SLE. Semin Immunopathol. 2014;36(3):365–375.
   PubMed Web of Science ®Google Scholar
• Jackson SW, Kolhatkar NS, Rawlings DJ. B cells take the front seat: dysregulated B cell signals orchestrate loss of tolerance and autoantibody production. Curr Opin Immunol. 2015;33:70–77.
   PubMed Web of Science ®Google Scholar
• Moulton VR, Tsokos GC. T cell signaling abnormalities contribute to aberrant immune cell function and autoimmunity. J Clin Invest. 2015;125(6):2220–2227.
   PubMed Web of Science ®Google Scholar
• Zhang J, Jacobi AM, Wang T, et al. Polyreactive autoantibodies in systemic lupus erythematosus have pathogenic potential. J Autoimmun. 2009;33(3–4):270–274.
   PubMed Web of Science ®Google Scholar
• Malik M, Arora P, Sachdeva R, et al. Elucidation of the potential disease-promoting influence of IgM apoptotic cell-reactive antibodies in lupus. Lupus. 2016;25(7):684–698.
   PubMed Web of Science ®Google Scholar
• Sigdel KR, Duan L, Wang Y, et al. Serum cytokines Th1, Th2, and Th17 expression profiling in active lupus nephritis-IV: from a southern Chinese Han population. Mediators Inflamm. 2016;2016:1.
   Web of Science ®Google Scholar
• Guimaraes PM, Scavuzzi BM, Stadtlober NP, et al. Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles. Immunol Cell Biol. 2017;95:824–831.
   PubMed Web of Science ®Google Scholar
• Ferreira VL, Borba HHL, Bonetti ADF, et al. Cytokines and interferons: types and functions. In: Khan WA, editor. Autoantibodies and cytokines. London: IntechOpen; 2018.
   Google Scholar
• Jandl C, King C. Cytokines in the germinal center niche. Antibodies. 2016;5(1):5.
   Web of Science ®Google Scholar
• Holdsworth SR, Gan PY. Cytokines: names and numbers you should care about. Clin J Am Soc Nephrol. 2015;10(12):2243–2254.
   PubMed Web of Science ®Google Scholar
• Zen M, Ghirardello A, Iaccarino L, et al. Hormones, immune response, and pregnancy in healthy women and SLE patients. Swiss Med Wkly. 2010;140(13–14):187–201.
   PubMed Web of Science ®Google Scholar
• Gaffen SL. An overview of IL-17 function and signaling. Cytokine. 2008;43(3):402–407.
   PubMed Web of Science ®Google Scholar
• Gu C, Wu L, Li X. IL-17 family: cytokines, receptors and signaling. Cytokine. 2013;64(2):477–485.
   PubMed Web of Science ®Google Scholar
• Crow MK, Kirou KA, Niewold TB. Cytokines in lupus. In: Wallace DJ, Hahn BH, editors. Dubois’ lupus erythematosus and related syndromes. Amsterdam, Netherlands: Elsevier; 2019. p. 137–152.
   Google Scholar
• Chasset F, Arnaud L. Targeting interferons and their pathways in systemic lupus erythematosus. Autoimmun Rev. 2018;17(1):44–52.
   PubMed Web of Science ®Google Scholar
• Mohamed AA, Gheita TA. Interferons, B cells and neutrophils: innate and adaptive allies in systemic lupus erythematosus. J Rheumatol Arthritic Dis. 2018;3(2):1.
   Google Scholar
• Garcia-Posadas L, Hodges RR, Li D, et al. Interaction of IFN-gamma with cholinergic agonists to modulate rat and human goblet cell function. Mucosal Immunol. 2016;9(1):206–217.
   PubMed Web of Science ®Google Scholar
• Zorn E, Nelson EA, Mohseni M, et al. IL-2 regulates FOXP3 expression in human CD4 + CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood. 2006;108(5):1571–1579.
   PubMed Web of Science ®Google Scholar
• Heiler S, Lotscher J, Kreuzaler M, et al. Prophylactic and therapeutic effects of interleukin-2 (IL-2)/Anti-IL-2 complexes in systemic lupus erythematosus-like chronic graft-versus-host disease. Front Immunol. 2018;9:656.
   PubMed Web of Science ®Google Scholar
• Borriello F, Iannone R, Somma SD, et al. GM-CSF and IL-3 modulate human monocyte TNF-alpha production and renewal. Front Immunol. 2016;7:680.
   PubMed Web of Science ®Google Scholar
• Borriello F, Galdiero MR, Varricchi G, et al. Innate immune modulation by GM-CSF and IL-3 in health and disease. Int J Mol Sci. 2019;20:834.
   Web of Science ®Google Scholar
• Ifergan I, Davidson TS, Kebir H, et al. Targeting the GM-CSF receptor for the treatment of CNS autoimmunity. J Autoimmun. 2017;84:1–11.
   PubMed Web of Science ®Google Scholar
• Bhattacharya P, Thiruppathi M, Elshabrawy HA, et al. GM-CSF: an immune modulatory cytokine that can suppress autoimmunity. Cytokine. 2015;75(2):261–271.
   PubMed Web of Science ®Google Scholar
• Al-Kholy W, Elsaid A, Sleem A, et al. TNF-alpha - 308 G > A and IFN-gamma + 874 A > T gene polymorphisms in Egyptian patients with lupus erythematosus. Meta Gene. 2016;9:137–141.
   PubMedGoogle Scholar
• Tahernia L, Namazi S, Rezaei N, et al. Cytokines in systemic lupus erythematosus: their role in pathogenesis of disease and possible therapeutic opportunities. Rheum Res. 2017;2(1):1–9.
   Google Scholar
• Buhrmann C, Yazdi M, Popper B, et al. Resveratrol chemosensitizes TNF-β-induced survival of 5-FU-treated colorectal cancer cells. Nutrients. 2018;10(7):888.
   Web of Science ®Google Scholar
• Buhrmann C, Yazdi M, Popper B, et al. Evidence that TNF-β induces proliferation in colorectal cancer cells and resveratrol can down-modulate it. Exp Biol Med (Maywood). 2019;244:1–12.
   PubMed Web of Science ®Google Scholar
• de Matos LG, Cândido EB, Vidigal PV, et al. Association between toll-like receptor and tumor necrosis factor immunological pathways in uterine cervical neoplasms. Tumori J. 2017;103(1):81–86.
   PubMed Web of Science ®Google Scholar
• Bosurgi L, Cao YG, Cabeza-Cabrerizo M, et al. Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells. Science. 2017;356(6342):1072–1076.
   PubMed Web of Science ®Google Scholar
• Xia F, Deng C, Jiang Y, et al. IL4 (interleukin 4) induces autophagy in B cells leading to exacerbated asthma. Autophagy. 2018;14(3):450–464.
   PubMed Web of Science ®Google Scholar
• Bagnasco D, Ferrando M, Varricchi G, et al. Anti-interleukin 5 (IL-5) and IL-5Ra biological drugs: efficacy, safety, and future perspectives in severe eosinophilic asthma. Front Med (Lausanne). 2017;4:135.
   PubMed Web of Science ®Google Scholar
• Liddament M, Husten J, Estephan T, et al. Higher binding affinity and in vitro potency of reslizumab for interleukin-5 compared with mepolizumab. Allergy Asthma Immunol Res. 2019;11(2):291–298.
   PubMed Web of Science ®Google Scholar
• Roufosse F. Targeting the interleukin-5 pathway for treatment of eosinophilic conditions other than asthma. Front Med (Lausanne). 2018;5:49.
   PubMed Web of Science ®Google Scholar
• Wallace DJ, Strand V, Merrill JT, et al. Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: a phase II dose-ranging randomised controlled trial. Ann Rheum Dis. 2017;76(3):534–542.
   PubMed Web of Science ®Google Scholar
• Katkam SK, Rajasekhar L, Kumaraswami K, et al. Association of IL -6 -174 G > C polymorphism with the risk of SLE among south Indians: evidence from case-control study and meta-analysis. Lupus. 2017;26(14):1491–1501.
   PubMed Web of Science ®Google Scholar
• Godsell J, Rudloff I, Kandane-Rathnayake R, et al. Clinical associations of IL-10 and IL-37 in systemic lupus erythematosus. Sci Rep. 2016;6(1):34604.
   PubMedGoogle Scholar
• Mohammadi S, Saghaeian Jazi M, Zare Ebrahimabad M, et al. Interleukin 10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population. Int J Immunogenet. 2019;46(1):20–30.
   PubMed Web of Science ®Google Scholar
• Wang X, Wong K, Ouyang W, et al. Targeting IL-10 family cytokines for the treatment of human diseases. Cold Spring Harb Perspect Biol. 2019;11(2):a028548.
   PubMed Web of Science ®Google Scholar
• Mao YM, Zhao CN, Leng J, et al. Interleukin-13: a promising therapeutic target for autoimmune disease. Cytokine Growth Factor Rev. 2019;45:9–23.
   PubMed Web of Science ®Google Scholar
• Tripp CS, Cuff C, Campbell AL, et al. RPC4046, a novel anti-interleukin-13 antibody, blocks IL-13 binding to IL-13 alpha1 and alpha2 receptors: a randomized, double-blind, placebo-controlled, dose-escalation first-in-human study. Adv Ther. 2017;34(6):1364–1381.
   PubMed Web of Science ®Google Scholar
• Bao K, Reinhardt RL. The differential expression of IL-4 and IL-13 and its impact on type-2 immunity. Cytokine. 2015;75(1):25–37.
   PubMed Web of Science ®Google Scholar
• Gwiggner M, Martinez-Nunez R, Whiteoak S, et al. MicroRNA-31 and MicroRNA-155 are overexpressed in ulcerative colitis and regulate IL-13 signaling by targeting interleukin 13 receptor α-1. Genes. 2018;9(2):85.
   Web of Science ®Google Scholar
• Gotovac JR, Fujihara KM, Phillips WA, et al. TGF-beta signaling and its targeted therapy in gastrointestinal cancers. Discov Med. 2018;26(142):103–112.
   PubMed Web of Science ®Google Scholar
• Esebanmen GE, Langridge WH. The role of TGF-beta signaling in dendritic cell tolerance. Immunol Res . 2017;65(5):987–994.
   PubMed Web of Science ®Google Scholar
• Correll KA, Edeen KE, Zemans RL, et al. TGF beta inhibits expression of SP-A, SP-B, SP-C, but not SP-D in human alveolar type II cells. Biochem Biophys Res Commun. 2018;499(4):843–848.
   PubMed Web of Science ®Google Scholar
• Vogel LA, Lester TL, Van Cleave VH, et al. Inhibition of murine B1 lymphocytes by interleukin‐12. Eur J Immunol. 1996;26(1):219–223.
   PubMed Web of Science ®Google Scholar
• Larosa M, Zen M, Gatto M, et al. IL-12 and IL-23/Th17 axis in systemic lupus erythematosus. Exp Biol Med (Maywood). 2019;244(1):42–51.
   PubMed Web of Science ®Google Scholar
• Chen D, Chen Y, Wen M, et al. The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis. Lupus. 2012;21(13):1385–1396.
   PubMed Web of Science ®Google Scholar
• Eagar TN, Miller SD. Helper T-cell subsets and control of the inflammatory response. In: Rich RR, Fleisher TA, Shearer WT, et al., editors. Clinical immunology. 5th ed. Amsterdam, Netherlands: Elsevier; 2019. p. 235–245. e231.
   Google Scholar
• Lourenco EV, La Cava A. Cytokines in systemic lupus erythematosus. Curr Mol Med. 2009;9(3):242–254.
   PubMed Web of Science ®Google Scholar
• Obermoser G, Pascual V. The interferon-alpha signature of systemic lupus erythematosus. Lupus. 2010;19(9):1012–1019.
   PubMed Web of Science ®Google Scholar
• Ito T, Wang YH, Liu YJ. Plasmacytoid dendritic cell precursors/type I interferon-producing cells sense viral infection by Toll-like receptor (TLR) 7 and TLR9. Springer Semin Immunopathol. 2005;26(3):221–229.
   PubMed Web of Science ®Google Scholar
• Lövgren T, Eloranta ML, Kastner B, et al. Induction of interferon‐α by immune complexes or liposomes containing systemic lupus erythematosus autoantigen–and Sjögren's syndrome autoantigen–associated RNA. Arthritis Rheum. 2006;54:1917–1927.
   PubMed Web of Science ®Google Scholar
• Schoenemeyer A, Barnes BJ, Mancl ME, et al. The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling. J Biol Chem. 2005;280(17):17005–17012.
   PubMed Web of Science ®Google Scholar
• Hoshino K, Sugiyama T, Matsumoto M, et al. IκB kinase-α is critical for interferon-α production induced by Toll-like receptors 7 and 9. Nature. 2006;440(7086):949.
   PubMed Web of Science ®Google Scholar
• Kawai T, Sato S, Ishii KJ, et al. Interferon-α induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol. 2004;5(10):1061.
   PubMed Web of Science ®Google Scholar
• Löseke S, Grage‐Griebenow E, Heine H, et al. In vitro‐generated viral double‐stranded RNA in contrast to polyinosinic: polycytidylic acid induces interferon‐α in human plasmacytoid dendritic cells. Scand J Immunol. 2006;63:264–274.
   PubMed Web of Science ®Google Scholar
• Kennedy WP, Maciuca R, Wolslegel K, et al. Association of the interferon signature metric with serological disease manifestations but not global activity scores in multiple cohorts of patients with SLE. Lupus Sci Med. 2015;2(1):e000080.
   PubMed Web of Science ®Google Scholar
• Abdel Galil SM, El-Shafey AM, Abdul-Maksoud RS, et al. Interferon alpha gene expression and serum level association with low vitamin D levels in Egyptian female patients with systemic lupus erythematosus. Lupus. 2018;27(2):199–209.
   PubMed Web of Science ®Google Scholar
• Petri M, Fu W, Ranger A, et al. Association between changes in gene signatures expression and disease activity among patients with systemic lupus erythematosus. BMC Med Genomics. 2019;12(1):4.
   PubMedGoogle Scholar
• Catalina MD, Bachali P, Geraci NS, et al. Gene expression analysis delineates the potential roles of multiple interferons in systemic lupus erythematosus. Commun Biol. 2019;2(1):140.
   PubMedGoogle Scholar
• Torell F, Eketjall S, Idborg H, et al. Cytokine profiles in autoantibody defined subgroups of systemic lupus erythematosus. J Proteome Res. 2019;18:1208–1217.
   PubMed Web of Science ®Google Scholar
• Pollard KM, Cauvi DM, Toomey CB, et al. Interferon-γ and systemic autoimmunity. Discov Med. 2013;16(87):123.
   PubMed Web of Science ®Google Scholar
• Baudino L, da Silveira SA, Nakata M, et al. Molecular and cellular basis for pathogenicity of autoantibodies: lessons from murine monoclonal autoantibodies. Springer Semin Immunopathol. 2006;28(2):175–184.
   PubMed Web of Science ®Google Scholar
• Lee SK, Silva DG, Martin JL, et al. Interferon-γ excess leads to pathogenic accumulation of follicular helper T cells and germinal centers. Immunity. 2012;37(5):880–892.
   PubMed Web of Science ®Google Scholar
• Kim K, Cho SK, Sestak A, et al. Interferon-gamma gene polymorphisms associated with susceptibility to systemic lupus erythematosus. Ann Rheum Dis. 2010;69(6):1247–1250.
   PubMed Web of Science ®Google Scholar
• Hagberg N, Joelsson M, Leonard D, et al. The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-gamma production in T cells from patients with SLE. Ann Rheum Dis. 2018;77(7):1070–1077.
   PubMed Web of Science ®Google Scholar
• Dufour A, Bellac CL, Eckhard U, et al. C-terminal truncation of IFN-gamma inhibits proinflammatory macrophage responses and is deficient in autoimmune disease. Nat Commun. 2018;9(1):2416.
   PubMedGoogle Scholar
• Kokic V, Martinovic Kaliterna D, Radic M, et al. Association between vitamin D, oestradiol and interferon-gamma in female patients with inactive systemic lupus erythematosus: a cross-sectional study. J Int Med Res. 2018;46(3):1162–1171.
   PubMed Web of Science ®Google Scholar
• Domeier PP, Chodisetti SB, Soni C, et al. IFN-gamma receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity. J Exp Med. 2016;213(5):715–732.
   PubMed Web of Science ®Google Scholar
• Comte D, Karampetsou MP, Kis-Toth K, et al. Brief report: CD4+ T cells from patients with systemic lupus erythematosus respond poorly to exogenous interleukin-2. Arthritis Rheumatol. 2017;69(4):808–813.
   PubMed Web of Science ®Google Scholar
• Humrich JY, Riemekasten G. Low-dose interleukin-2 therapy for the treatment of systemic lupus erythematosus. Curr Opin Rheumatol. 2019;31(2):208–212.
   PubMed Web of Science ®Google Scholar
• Shao M, He J, Zhang R, et al. Interleukin-2 deficiency associated with renal impairment in systemic lupus erythematosus. J Interferon Cytokine Res. 2019;39(2):117–124.
   PubMed Web of Science ®Google Scholar
• Fontenot JD, Rasmussen JP, Gavin MA, et al. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol . 2005;6(11):1142.
   PubMed Web of Science ®Google Scholar
• D’Cruz LM, Klein L. Development and function of agonist-induced CD25+ Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol. 2005;6:1152.
   PubMed Web of Science ®Google Scholar
• Setoguchi R, Hori S, Takahashi T, et al. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med. 2005;201(5):723–735.
   PubMed Web of Science ®Google Scholar
• Liu X, Jing X, Wu X, et al. OP0043 The number of circulating regulatory t cells is reduced and low-dose il-2 selectively stimulates its proliferation in patients with systemic lupus erythematosus. Ann Rheum Dis. 2017;76:69.
   Web of Science ®Google Scholar
• Dai H, He F, Tsokos GC, et al. IL-23 limits the production of IL-2 and promotes autoimmunity in lupus. J Immunol. 2017;199(3):903–910.
   PubMed Web of Science ®Google Scholar
• Miyara M, Amoura Z, Parizot C, et al. Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol. 2005;175(12):8392–8400.
   PubMed Web of Science ®Google Scholar
• Suen JL, Li HT, Jong YJ, et al. Altered homeostasis of CD4+ FoxP3+ regulatory T‐cell subpopulations in systemic lupus erythematosus. Immunology. 2009;127(2):196–205.
   PubMed Web of Science ®Google Scholar
• Bonelli M, von Dalwigk K, Savitskaya A, et al. Foxp3 expression in CD4+ T cells of patients with systemic lupus erythematosus: a comparative phenotypic analysis. Ann Rheum Dis. 2007;67(5):664–671.
   PubMed Web of Science ®Google Scholar
• Ohl K, Tenbrock K. Regulatory T cells in systemic lupus erythematosus. Eur J Immunol. 2015;45(2):344–355.
   PubMed Web of Science ®Google Scholar
• Jones MB, Alvarez CA, Johnson JL, et al. CD45Rb-low effector T cells require IL-4 to induce IL-10 in FoxP3 Tregs and to protect mice from inflammation. PLoS One. 2019;14(5):e0216893.
   PubMed Web of Science ®Google Scholar
• Rosenzwajg M, Lorenzon R, Cacoub P, et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 2019;78(2):209–217.
   PubMed Web of Science ®Google Scholar
• von Spee-Mayer C, Siegert E, Abdirama D, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. 2016;75(7):1407–1415.
   PubMed Web of Science ®Google Scholar
• Fiehn C, Wermann M, Pezzutto A, et al. Plasma GM-CSF concentrations in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropathy. Z Rheumatol. 1992;51(3):121–126.
   PubMed Web of Science ®Google Scholar
• López P, Rodríguez‐Carrio J, Martínez A, et al. Senescent profile of angiogenic T cells from systemic lupus erythematosus patients. J Leukoc Biol. 2016;99:405–412.
   PubMed Web of Science ®Google Scholar
• López P, De Paz B, Rodríguez-Carrio J, et al. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep. 2016;6(1):24072.
   PubMedGoogle Scholar
• Chiewchengchol D, Midgley A, Sodsai P, et al. The protective effect of GM-CSF on serum-induced neutrophil apoptosis in juvenile systemic lupus erythematosus patients. Clin Rheumatol. 2015;34(1):85–91.
   PubMed Web of Science ®Google Scholar
• Derouet M, Thomas L, Cross A, et al. Granulocyte macrophage colony-stimulating factor signaling and proteasome inhibition delay neutrophil apoptosis by increasing the stability of Mcl-1. J Biol Chem. 2004;279(26):26915–26921.
   PubMed Web of Science ®Google Scholar
• Willeke P, Schluter B, Schotte H, et al. Increased frequency of GM-CSF secreting PBMC in patients with active systemic lupus erythematosus can be reduced by immunoadsorption. Lupus. 2004;13(4):257–262.
   PubMed Web of Science ®Google Scholar
• Yoshio T, Okamoto H, Kurasawa K, et al. IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus. Lupus. 2016;25(9):997–1003.
   PubMed Web of Science ®Google Scholar
• Lu C, Li J. Effect of G-CSF and GM-CSF on expression of TNF-alpha mRNA and CD69 and secretion of IgG in peripheral blood mononuclear cells from systemic lupus erythematosus patients. Zhongguo Shi Yan Xue ye Xue za Zhi. 2002;10(6):531–534.
   PubMedGoogle Scholar
• Enzler T, Gillessen S, Manis JP, et al. Deficiencies of GM-CSF and interferon γ link inflammation and cancer. J Exp Med. 2003;197(9):1213–1219.
   PubMed Web of Science ®Google Scholar
• Ahmed HH, Taha FM, Darweesh HES, et al. Association between TNF promoter− 308 G > A and LTA 252 A > G polymorphisms and systemic lupus erythematosus. Mol Biol Rep. 2014;41(4):2029–2036.
   PubMed Web of Science ®Google Scholar
• Postal M, Appenzeller S. The role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of systemic lupus erythematosus. Cytokine. 2011;56(3):537–543.
   PubMed Web of Science ®Google Scholar
• Ma CY, Jiao YI, Zhang J, et al. Elevated plasma level of HMGB1 is associated with disease activity and combined alterations with IFN-alpha and TNF-alpha in systemic lupus erythematosus. Rheumatol Int. 2012;32(2):395–402.
   PubMed Web of Science ®Google Scholar
• Chatzidakis I, Mamalaki C. T cells as sources and targets of TNF: implications for immunity and autoimmunity. In: Kollias G, Sfikakis PP, editors. TNF pathophysiology. Basel, Switzerland: Karger Publishers; 2010. p. 105–118.
   Google Scholar
• Rageh IM, Sharaawy AA, Fouda AI, et al. Tumor necrosis factor-α promoter gene polymorphism (308 G/A) in the Egyptian patients with systemic lupus erythematosus. Benha Med J. 2017;34:5.
   Google Scholar
• Tahghighi F, Ziaee V, Moradinejad MH, et al. Tumor necrosis factor-alpha single nucleotide polymorphisms in juvenile systemic lupus erythematosus. Hum Immunol. 2015;76(8):533–536.
   PubMed Web of Science ®Google Scholar
• Umare VD, Pradhan VD, Rajadhyaksha AG, et al. Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients. Hum Immunol. 2017;78(2):201–208.
   PubMed Web of Science ®Google Scholar
• Brennan DC, Yui MA, Wuthrich RP, et al. Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury. J. Immunol. 1989;143(11):3470–3475.
   PubMed Web of Science ®Google Scholar
• Kontoyiannis D, Kollias G. Accelerated autoimmunity and lupus nephritis in NZB mice with an engineered heterozygous deficiency in tumor necrosis factor. Eur J Immunol. 2000;30(7):2038–2047.
   PubMed Web of Science ®Google Scholar
• Zhu LJ, Landolt-Marticorena C, Li T, et al. Altered expression of TNF-α signaling pathway proteins in systemic lupus erythematosus. J Rheumatol. 2010;37(8):1658–1666.
   PubMed Web of Science ®Google Scholar
• Nelms K, Keegan AD, Zamorano J, et al. The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol. 1999;17(1):701–738.
   PubMed Web of Science ®Google Scholar
• Yu H, Liu P, Lin Y, et al. Interleukin 4 and STAT6 gene polymorphisms are associated with systemic lupus erythematosus in Chinese patients. Lupus. 2010;19(10):1219–1228.
   PubMed Web of Science ®Google Scholar
• Elewa EA, Zakaria O, Mohamed EI, et al. The role of interleukins 4, 17 and interferon gamma as biomarkers in patients with Systemic Lupus Erythematosus and their correlation with disease activity. Egypt Rheumatol. 2014;36(1):21–27.
   Google Scholar
• Mohammadoo-Khorasani M, Salimi S, Tabatabai E, et al. Interleukin-1beta (IL-1beta) & IL-4 gene polymorphisms in patients with systemic lupus erythematosus (SLE) & their association with susceptibility to SLE. Indian J Med Res. 2016;143:591–596.
   PubMed Web of Science ®Google Scholar
• Mohsen IH. Study polymorphisms of IL-4 gene using PCR-SSCP technique in Iraqi systemic lupus erthymatous patients. J Pharm Sci Res. 2018;10:613–614.
   Google Scholar
• Deocharan B, Marambio P, Edelman M, et al. Differential effects of interleukin-4 in peptide induced autoimmunity. Clin Immunol. 2003;108(2):80–88.
   PubMed Web of Science ®Google Scholar
• Carneiro JRM, Fuzii HT, Kayser C, et al. IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions. Clinics. 2011;66(1):77–82.
   PubMed Web of Science ®Google Scholar
• Zhu H, Mi W, Luo H, et al. Whole-genome transcription and DNA methylation analysis of peripheral blood mononuclear cells identified aberrant gene regulation pathways in systemic lupus erythematosus. Arthritis Res Ther. 2016;18:162.
   PubMed Web of Science ®Google Scholar
• Timóteo RP, Micheli DC, Teodoro RB, et al. Characterization of inflammatory markers associated with systemic lupus erythematosus patients undergoing treatment. Rev Bras Reumatol. 2016;56(6):497–503.
   Google Scholar
• Wen X, Zhang D, Kikuchi Y, et al. Transgene‐mediated hyper‐expression of IL‐5 inhibits autoimmune disease but increases the risk of B cell chronic lymphocytic leukemia in a model of murine lupus. Eur J Immunol. 2004;34(10):2740–2749.
   PubMed Web of Science ®Google Scholar
• Jones BE, Maerz MD, Buckner JH. IL-6: a cytokine at the crossroads of autoimmunity. Curr Opin Immunol. 2018;55:9–14.
   PubMed Web of Science ®Google Scholar
• Mellor ‐Pita S, Citores MJ, Castejon R, et al. Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus. Cytometry B Clin Cytom. 2009;76:261–270.
   PubMedGoogle Scholar
• Thanadetsuntorn C, Ngamjanyaporn P, Setthaudom C, et al. The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus. Sci Rep. 2018;8(1):2620.
   PubMedGoogle Scholar
• Umare V, Nadkarni A, Nadkar M, et al. Do high sensitivity C-reactive protein and serum interleukin-6 levels correlate with disease activity in systemic lupus erythematosuspatients? J Postgrad Med. 2017;63:92–95.
   PubMed Web of Science ®Google Scholar
• Bashlakova N, Tyabut T, Buglova A. AB0048 Antiphospholipid antibodies, interleukin-6 and tumor necrosis factor-α in atherosclerotic process in patients with rheumatoid arthritis and systemic lupus erythematosus. London: BMJ Publishing Group Ltd; 2017.
   Google Scholar
• Wan Asyraf WA, Mohd Shahrir MS, Asrul W, et al. The association between serum prolactin levels and interleukin-6 and systemic lupus erythematosus activity. Reumatismo. 2018;70(4):241–250.
   PubMed Web of Science ®Google Scholar
• Cai XY, Lu Y, Tang C, et al. Effect of interleukin-6 promoter DNA methylation on the pathogenesis of systemic lupus erythematosus. Zhonghua Yi Xue Za Zhi. 2017;97(19):1491–1495.
   PubMedGoogle Scholar
• Stannard JN, Reed TJ, Myers E, et al. Lupus skin is primed for IL-6 inflammatory responses through a keratinocyte-mediated autocrine type I interferon loop. J Invest Dermatol. 2017;137(1):115–122.
   PubMed Web of Science ®Google Scholar
• Cash H, Relle M, Menke J, et al. Interleukin 6 (IL-6) deficiency delays lupus nephritis in MRL-Faslpr mice: the IL-6 pathway as a new therapeutic target in treatment of autoimmune kidney disease in systemic lupus erythematosus. J Rheumatol. 2010;37(1):60–70.
   PubMed Web of Science ®Google Scholar
• Grau Garcia E, Ortiz-Sanjuan F, Fernandez Matilla M, et al. Systemic lupus erythematosus patients with positives autoantibodies with remission or low activity exhibit both lower interferon alpha and interleukin-10 levels. Lupus. 2018;5(1):PS2:30.
   Google Scholar
• Grammatikos AP, Kyttaris VC, Kis-Toth K, et al. AT cell gene expression panel for the diagnosis and monitoring of disease activity in patients with systemic lupus erythematosus. Clin Immunol. 2014;150(2):192–200.
   PubMed Web of Science ®Google Scholar
• Ouyang W, Rutz S, Crellin NK, et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol. 2011;29(1):71–109.
   PubMedGoogle Scholar
• Dörner T, Jacobi AM, Lipsky PE. B cells in autoimmunity. Arthritis Res Ther. 2009;11:247.
   PubMed Web of Science ®Google Scholar
• Peng H, Wang W, Zhou M, et al. Role of interleukin-10 and interleukin-10 receptor in systemic lupus erythematosus. Clin Rheumatol. 2013;32(9):1255–1266.
   PubMed Web of Science ®Google Scholar
• Hayashi T. Therapeutic strategies for SLE involving cytokines: mechanism-oriented therapies especially IFN. BioMed Res Int. 2010;2010:19.
   Google Scholar
• Bassiouny M, Sonbol A, Eissa H, et al. CD4+ Foxp3+ T cells, interleukin-35 (IL-35) and IL-10 in systemic lupus erythematosus patients: relation to disease activity. Egypt Rheumatol. 2018;41(3):209–214.
   Web of Science ®Google Scholar
• Zhou H, Hu B, Huang N, et al. Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus. Clin Rheumatol. 2018;37(9):2405–2413.
   PubMed Web of Science ®Google Scholar
• Llorente L, Zou W, Levy Y, et al. Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med. 1995;181(3):839–844.
   PubMed Web of Science ®Google Scholar
• Yuan Y, Wang X, Ren L, et al. Associations between interleukin-10 gene polymorphisms and systemic lupus erythematosus risk: a meta-analysis with trial sequential analysis. Clin Exp Rheumatol. 2018;37:242–253.
   PubMed Web of Science ®Google Scholar
• Teichmann LL, Kashgarian M, Weaver CT, et al. B cell-derived IL-10 does not regulate spontaneous systemic autoimmunity in MRL. Faslpr mice. J Immunol. 2012;188(2):678–685.
   PubMed Web of Science ®Google Scholar
• May RD, Fung M. Strategies targeting the IL-4/IL-13 axes in disease. Cytokine. 2015;75(1):89–116.
   PubMed Web of Science ®Google Scholar
• Arkatkar T, Du SW, Jacobs HM, et al. B cell–derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity. J Exp Med. 2017;214(11):3207–3217.
   PubMed Web of Science ®Google Scholar
• Spadaro A, Rinaldi T, Riccieri V, et al. Interleukin-13 in autoimmune rheumatic diseases: relationship with the autoantibody profile. Clin Exp Rheumatol. 2002;20(2):213–216.
   PubMed Web of Science ®Google Scholar
• Morimoto S, Tokano Y, Kaneko H, et al. The increased interleukin-13 in patients with systemic lupus erythematosus: relations to other Thl-, Th2-related cytokines and clinical findings. Autoimmunity. 2001;34(1):19–25.
   PubMed Web of Science ®Google Scholar
• Zusen X, Yanlei C. Determination of serum interleukin-13 and nerve growth factor in patients with systemic lupus erythematosus and clinical significance. J Huazhong Univ Sci Technol Med Sci. 2005;25(3):360–361.
   PubMedGoogle Scholar
• Brugos B, Vincze Z, Sipka S, et al. Serum and urinary cytokine levels of SLE patients. Pharmazie. 2012;67:411–413.
   PubMed Web of Science ®Google Scholar
• Wang R, Lu YL, Huang HT, et al. Association of interleukin 13 gene polymorphisms and plasma IL 13 level with risk of systemic lupus erythematosus. Cytokine. 2018;104:92–97.
   PubMed Web of Science ®Google Scholar
• Becker-Merok A, Eilertsen GØ, Nossent JC. Levels of transforming growth factor-β are low in systemic lupus erythematosus patients with active disease. J Rheumatol. 2010;37(10):2039–2045.
   PubMed Web of Science ®Google Scholar
• El Menyawi M, Fawzy M, Habib M, et al. Serum transforming growth factor-beta 1 level in Egyptian systemic lupus erythematosus patients. Arch Rheumatol. 2018;33(3):358.
   PubMed Web of Science ®Google Scholar
• Jin T, Almehed K, Carlsten H, et al. Decreased serum levels of TGF-β1 are associated with renal damage in female patients with systemic lupus erythematosus. Lupus. 2012;21(3):310–318.
   PubMed Web of Science ®Google Scholar
• 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. Eur Cytokine Netw. 2013;24:69–74.
   PubMed Web of Science ®Google Scholar
• Raymond WD, Eilertsen GØ, Nossent J. Principal component analysis reveals disconnect between regulatory cytokines and disease activity in systemic lupus erythematosus. Cytokine. 2019;114:67.
   PubMed Web of Science ®Google Scholar
• Metawie SA, ElRefai RM, ElAdle SS, et al. Transforming growth factor-β1 in systemic lupus erythematosus patients and its relation to organ damage and disease activity. Egypt Rheumatol. 2015;37(4):S49–S54.
   Web of Science ®Google Scholar
• Salam SMA, Saleh SH, El-Shahawy EE, et al. Assessment of plasma and urinary transforming growth factor beta 1 (TGF-β1) in children with lupus nephritis. Egypt J Pediatr Allergy Immunol. 2011;9:21–27.
   Google Scholar
• Yuan Y, Yang M, Wang K, et al. Excessive activation of the TLR9/TGF-β1/PDGF-B pathway in the peripheral blood of patients with systemic lupus erythematosus. Arthritis Res Ther. 2017;19:70.
   PubMed Web of Science ®Google Scholar
• Susianti H, Iriane VM, Dharmanata S, et al. Analysis of urinary TGF-β1, MCP-1, NGAL, and IL-17 as biomarkers for lupus nephritis. Pathophysiology. 2015;22(1):65–71.
   PubMedGoogle Scholar
• Torabinejad S, Mardani R, Habibagahi Z, et al. Urinary monocyte chemotactic protein-1 and transforming growth factor-β in systemic lupus erythematosus. Indian J Nephrol. 2012;22(1):5.
   PubMedGoogle Scholar
• Singh RR, Ebling FM, Albuquerque DA, et al. Induction of autoantibody production is limited in nonautoimmune mice. J Immunol. 2002;169(1):587–594.
   PubMed Web of Science ®Google Scholar
• Rekik R, Khanfir MS, Larbi T, et al. Impaired TGF-β signaling in patients with active systemic lupus erythematosus is associated with an overexpression of IL-22. Cytokine. 2018;108:182–189.
   PubMed Web of Science ®Google Scholar
• Saxena V, Lienesch DW, Zhou M, et al. Dual roles of immunoregulatory cytokine TGF-β in the pathogenesis of autoimmunity-mediated organ damage. J Immunol. 2008;180(3):1903–1912.
   PubMed Web of Science ®Google Scholar
• Talaat RM, Mohamed SF, Bassyouni IH, et al. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity. Cytokine. 2015;72(2):146–153.
   PubMed Web of Science ®Google Scholar
• Schmidt T, Luebbe J, Paust H-J, et al. Mechanisms and functions of IL-17 signaling in renal autoimmune diseases. Mol Immunol. 2018;104:90–99.
   PubMed Web of Science ®Google Scholar
• Martin JC, Baeten DL, Josien R. Emerging role of IL-17 and Th17 cells in systemic lupus erythematosus. Clin Immunol. 2014;154(1):1–12.
   PubMed Web of Science ®Google Scholar
• Hsu HC, Yang P, Wang J, et al. Interleukin 17–producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol. 2008;9(2):166.
   PubMed Web of Science ®Google Scholar
• Crispín JC, Oukka M, Bayliss G, et al. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol. 2008;181(12):8761–8766.
   PubMed Web of Science ®Google Scholar
• Wong CK, Lit LCW, Tam LS, et al. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol. 2008;127(3):385–393.
   PubMed Web of Science ®Google Scholar
• Yang J, Chu Y, Yang X, et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum. 2009;60:1472–1483.
   PubMed Web of Science ®Google Scholar
• Zhao XF, Pan HF, Yuan H, et al. Increased serum interleukin 17 in patients with systemic lupus erythematosus. Mol Biol Rep. 2010;37(1):81–85.
   PubMed Web of Science ®Google Scholar
• Li Y, Wang R, Liu S, et al. Interleukin-25 is upregulated in patients with systemic lupus erythematosus and ameliorates murine lupus by inhibiting inflammatory cytokine production. Int Immunopharmacol. 2019;74:105680.
   PubMed Web of Science ®Google Scholar
• Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201(2):233–240.
   PubMed Web of Science ®Google Scholar
• Aggarwal S, Ghilardi N, Xie M-H, et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278(3):1910–1914.
   PubMed Web of Science ®Google Scholar
• McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23–IL-17 immune pathway. Trends Immunol. 2006;27(1):17–23.
   PubMed Web of Science ®Google Scholar
• Fischer K, Przepiera-Będzak H, Sawicki M, et al. Serum interleukin-23 in Polish patients with systemic lupus erythematosus: association with lupus nephritis, obesity, and peripheral vascular disease. Mediat Inflamm. 2017;2017:1.
   Web of Science ®Google Scholar
• Shahin D, El-Farahaty R, Houssen M, et al. Serum 25-OH vitamin D level in treatment-naïve systemic lupus erythematosus patients: relation to disease activity, IL-23 and IL-17. Lupus. 2017;26(9):917–926.
   PubMed Web of Science ®Google Scholar
• Ghanima ATA, Elolemy GG, Ganeb SS, et al. Role of T helper 17 cells in the pathogenesis of systemic lupus erythematosus. Egypt J Immunol. 2012;19:25–33.
   PubMedGoogle Scholar
• Dai H, Kyttaris VC. Inhibition of IL-23/IL-23 Receptor signaling ameliorates disease in lupus-prone mice by decreasing the generation of DN T cells. Am Assoc Immnol. 2016;196(1).
   Google Scholar
• Italiani P, Manca ML, Angelotti F, et al. IL-1 family cytokines and soluble receptors in systemic lupus erythematosus. Arthritis Res Ther. 2018;20(1):27–36.
   PubMed Web of Science ®Google Scholar
• Cheng Y, Yang X, Zhang X, et al. Analysis of expression levels of IL-17 and IL-34 and influencing factors for prognosis in patients with lupus nephritis. Exp Ther Med. 2019;17:2279–2283.
   PubMed Web of Science ®Google Scholar
• Mende R, Vincent FB, Kandane-Rathnayake R, et al. Analysis of Serum Interleukin (IL)-1beta and IL-18 in systemic lupus erythematosus. Front Immunol. 2018;9:1250.
   PubMed Web of Science ®Google Scholar
• Xie HH, Shen H, Zhang L, et al. Elevated serum interleukin-34 level in patients with systemic lupus erythematosus is associated with disease activity. Sci Rep. 2018;8(1):3462.
   PubMedGoogle Scholar
• Chu M, Wong CK, Cai Z, et al. Elevated expression and pro-inflammatory activity of IL-36 in patients with systemic lupus erythematosus. Molecules. 2015;20(10):19588–19604.
   PubMed Web of Science ®Google Scholar
• He D, Liu M, Liu B. Interleukin-35 as a new biomarker of renal involvement in lupus nephritis patients. Tohoku J Exp Med. 2018;244(4):263–270.
   PubMed Web of Science ®Google Scholar
• Ye L, Ji L, Wen Z, et al. IL-37 inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells of patients with systemic lupus erythematosus: its correlation with disease activity. J Transl Med. 2014;12(1):69.
   PubMedGoogle Scholar
• Kalunian KC, Merrill JT, Maciuca R, et al. A Phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-α) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis. 2016;75(1):196–202.
   PubMed Web of Science ®Google Scholar
• Khamashta M, Merrill JT, Werth VP, et al. Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016;75(11):1909–1916.
   PubMed Web of Science ®Google Scholar
• Isenberg DA, Merrill JT. Why, why, why de-lupus (does so badly in clinical trials). Expert Rev Clin Immunol. 2016;12:95–98. 
   Web of Science ®Google Scholar
• AdisInsight. Sifalimumab. 2018. https://adisinsight.springer.com/drugs/800024071 (Accessed on 26th October 2019).
   Google Scholar
• Furie R, Khamashta M, Merrill JT, et al. Anifrolumab, an anti–interferon‐α receptor monoclonal antibody, in moderate‐to‐severe systemic lupus erythematosus. Arthriti Rheumatol. 2017;69:376–386.
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. Efficacy and safety of anifrolumab compared to placebo in adult subjects with active systemic lupus erythematosus. Bethesda (MD): ClinicalTrials.gov.; 2015.
   Google Scholar
• AstraZeneca. Update on TULIP 1 Phase III trial for anifrolumab in systemic lupus erythematosus. Cambridge: AstraZeneca; 2018.
   Google Scholar
• ClinicalTrials.gov. Induction of regulatory t cells by low dose il2 in autoimmune and inflammatory diseases (TRANSREG). Bethesda (MD): ClinicalTrials.gov; 2013.
   Google Scholar
• ClinicalTrials.gov. Low-dose interleukin-2 for treatment of systemic lupus erythematosus (Charact-IL-2). Bethesda (MD): ClinicalTrials.gov; 2017.
   Google Scholar
• ClinicalTrials.gov. ILT-101 in patients with active moderate to severe systemic lupus erythematosus (SLE) (LUPIL-2). Bethesda (MD): ClinicalTrials.gov; 2016.
   Google Scholar
• van Vollenhoven RF, Hahn BH, Tsokos GC, et al. Efficacy and safety of ustekinumab, an IL-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a multicentre, double-blind, phase 2, randomised, controlled study. Lancet. 2018;392(10155):1330–1339.
   PubMed Web of Science ®Google Scholar