rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2015-493-501rsp-2126Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHИнтерлейкин 23 у больных системными васкулитами, ассоциированными с антинейтрофильными цитоплазматическими антителами: собственные результаты и обзор литературыINTERLEUKIN-23 IN PATIENTS WITH ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED SYSTEMIC VASCULITIDES: THE AUTHORS’ RESULTS AND A REVIEW OF LITERATUREБекетоваТ. В.BeketovaT. V.tvbek@rambler.ruАлександроваЕ. Н.AleksandrovaE. N.НиконороваН. О.NikonorovaN. O.ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва, Россия 115522 Москва, Каширское шоссе, 34АРоссияV.A. Nasonova Research Institute of Rheumatology, Moscow, Russia 34A, Kashirskoe Shosse, Moscow 115522Russian Federation201514102015535493501Copyright © Бекетова Т.В., Александрова Е.Н., Никонорова Н.О., 20152015Бекетова Т.В., Александрова Е.Н., Никонорова Н.О.Beketova T.V., Aleksandrova E.N., Nikonorova N.O.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2126

В патогенезе системных васкулитов, ассоциированных с антинейтрофильными цитоплазматическими антителами (АНЦА-СВ), могут участвовать клеточные реакции, опосредованные Т-хелперами 17-го типа (Th17). Мы изучали зависимость клинических параметров от содержания в сыворотке крови больных АНЦА-СВ интерлейкина 23 (ИЛ23), принимающего участие в реализации Th17-ответа, а также влияние терапии на этот показатель.

Цель – исследовать концентрацию ИЛ23 в сыворотке крови больных АНЦА-СВ с различной активностью заболевания и разным индукционным лечением в сравнении со здоровыми донорами.

Материал и методы

Материал и методы. При помощи иммуноферментного анализа (ИФА) исследована концентрация ИЛ23 у 40 больных АНЦА-СВ [медиана возраста – 44 года (от 20 до 65 лет); соотношение женщины/мужчины – 1,11] и 8 здоровых доноров [медиана возраста 47 лет (от 21 года до 66 лет); соотношение женщины/мужчины – 1,67]. У 23 пациентов АНЦА-СВ был классифицирован как гранулематоз с полиангиитом, у 14 – как микроскопический полиангиит и у 3 – как эозинофильный гранулематоз с полиангиитом. В активную стадию АНЦА-СВ были обследованы 26 больных, в период ремиссии – 28 (у 22 из 28 ремиссия была индуцирована ритуксимабом). Проанализирована связь между концентрацией ИЛ23 и активностью заболевания, особенностями клинического течения АНЦА-СВ.

Результаты и обсуждение

Результаты и обсуждение. Статистически достоверное повышение концентрации сывороточного ИЛ23 в сравнении со здоровыми донорами отмечено только у больных с дебютом АНЦА-СВ, не получавших лечения (медиана 41,9 и 13,1 пг/мл соответственно; p<0,05). Применение как иммуносупрессивной, так и анти -В-клеточной терапии стойко снижало сывороточную концентрацию ИЛ23 (до 5,2–8,8 пг/мл).

Заключение

Заключение. Перспективно дальнейшее изучение ИЛ23 и функционально близких ему цитокинов при АНЦА-СВ.

T helper type 17 (Th17) cell-mediated reactions can be implicated in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitides (SV) (ANCA-SV). The relationship of clinical parameters to the serum levels of interleukin-23 (IL-23) that is involved in a Th17 response and the impact of therapy on this factor were studied in patients with ANCA-SV.

Objective

Objective: to study serum IL-23 concentrations in patients having varying ANCA-SV activities and different induction treatment regimens as compared to healthy donors.

Subjects and methods

Subjects and methods. Enzyme immunoassay was used to investigate IL-23 concentrations in 40 patients with ANCA-SV [median age, 44 years (20 to 65 years); female/male ratio, 1.11] and 8 healthy donors [median age, 47 years (21 to 66 years); female/male ratio, 1.67]. ANCA-SV was classified as granulomatosis with polyangiitis in 23 patients, as microscopic polyangiitis in 14, and as eosinophilic granulomatosis with polyangiitis in 3. Examinations were made in 26 patients with ANCA-SV in active stage and in 28 in remission (induced with rituximab in 22 of the 28 patients). The association was analyzed between IL-23 concentrations and disease activity, as well as clinical features of ANCA-SV.

Results and discussion

Results and discussion. Significantly elevated serum IL-23 concentrations were noted only in the untreated patients at the onset of ANCA-SV as compared to the healthy donors (median 41.9 and 13.1 pg/ml, respectively; p < 0.05). Both immunosuppressive and anti-B-cell therapy persistently decreased serum IL-23 concentrations (to 5.2–88 pg/ml).

Conclusion

Conclusion. Further investigation of IL-23 and functionally related cytokines in ANCA-SV is promising

системные васкулитыантинейтрофильные цитоплазматические антителацитокиныинтерлейкин 23Т-хелперы 17-го типаsystemic vasculitidesantineutrophil cytoplasmic antibodiescytokinesinterleukin-23T helper type 17 cells.ReferencesHuh JR, Littman DR. Small molecule inhibitors of RORgammat: targeting Th17 cells and other applications. Eur J Immunol. 2012;42(9):2232–7. doi: 10.1002/eji.201242740Huh JR, Littman DR. Small molecule inhibitors of RORgammat: targeting Th17 cells and other applications. Eur J Immunol. 2012;42(9):2232–7. doi: 10.1002/eji.201242740Abdulahad WH, Lamprecht P, Kallenberg CG. T-helper cells as new players in ANCA-associated vasculitides. Arthritis Res Ther. 2011;13:236. doi: 10.1186/ar3362Abdulahad WH, Lamprecht P, Kallenberg CG. T-helper cells as new players in ANCA-associated vasculitides. Arthritis Res Ther. 2011;13:236. doi: 10.1186/ar3362Aggarwal S, Ghilardi N, Xie MH, et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278:1910–4. doi: 10.1074/jbc.M207577200Aggarwal S, Ghilardi N, Xie MH, et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278:1910–4. doi: 10.1074/jbc.M207577200Teunissen MBM, Koomen CW, de Waal Malefit R, et al. Interleukin-17 and interferon-synergize in enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol.1998;111:645–9. doi: 10.1046/j.1523-1747.1998.00347.xTeunissen MBM, Koomen CW, de Waal Malefit R, et al. Interleukin-17 and interferon-synergize in enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol.1998;111:645–9. doi: 10.1046/j.1523-1747.1998.00347.xKastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol. 2007;25:221–42. doi: 10.1146/annurev.immunol.22.012703.104758Kastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol. 2007;25:221–42. doi: 10.1146/annurev.immunol.22.012703.104758Duvallet E, Semerano L, Assier E, et al. Interleukin-23: A key cytokine in inflammatory diseases. Ann Med. 2011;43(7):503–11. doi: 10.3109/07853890.2011.577093Duvallet E, Semerano L, Assier E, et al. Interleukin-23: A key cytokine in inflammatory diseases. Ann Med. 2011;43(7):503–11. doi: 10.3109/07853890.2011.577093Корсакова ЮЛ, Станислав МЛ, Денисов ЛН, Насонов ЕЛ. Устекинумаб – новый препарат для лечения псориаза и псориатического артрита. Научно-практическая ревматология. 2013;51(2):170–80 [Korsakova YuL, Stanislav ML, Denisov LN, Nasonov EL. Ustekinumab – a new drug for the treatment of psoriasis and psoriatic arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(2):170–80 (In Russ.)].Корсакова ЮЛ, Станислав МЛ, Денисов ЛН, Насонов ЕЛ. Устекинумаб – новый препарат для лечения псориаза и псориатического артрита. Научно-практическая ревматология. 2013;51(2):170–80 [Korsakova YuL, Stanislav ML, Denisov LN, Nasonov EL. Ustekinumab – a new drug for the treatment of psoriasis and psoriatic arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(2):170–80 (In Russ.)].Tuskey A, Behm BW. Profile of ustekinumab and its potential in patients with moderate-to-severe Crohn’s disease. Clin Exper Gastroenterol. 2014;7:173–9.Tuskey A, Behm BW. Profile of ustekinumab and its potential in patients with moderate-to-severe Crohn’s disease. Clin Exper Gastroenterol. 2014;7:173–9.Toussirot E, Michel F, Bereau M, Binda D. Ustekinumab in chronic immune-mediated diseases: a review of long term safety and patient improvement. Patient Рrefer Аdherence. 2013;7:369–77. doi: 10.2147/PPA.S33162Toussirot E, Michel F, Bereau M, Binda D. Ustekinumab in chronic immune-mediated diseases: a review of long term safety and patient improvement. Patient Рrefer Аdherence. 2013;7:369–77. doi: 10.2147/PPA.S33162McKinney EF, Willcocks LC, Broecker V, Smith KGC. The immunopathology of ANCA-associated vasculitis. Semin Immunopathol. 2014;36(4):461–78. doi: 10.1007/s00281-014- 0436-6McKinney EF, Willcocks LC, Broecker V, Smith KGC. The immunopathology of ANCA-associated vasculitis. Semin Immunopathol. 2014;36(4):461–78. doi: 10.1007/s00281-014- 0436-6Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum. 1990;33:1101–7. doi: 10.1002/art.1780330807Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum. 1990;33:1101–7. doi: 10.1002/art.1780330807Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990;33:1094–100. doi: 10.1002/art.1780330806Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990;33:1094–100. doi: 10.1002/art.1780330806Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1–11. doi: 10.1002/art.37715Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1–11. doi: 10.1002/art.37715Watts R, Lane S, Hanslik T, et al. Development and validation of a consensus methodology for the classification of the ANCAassociated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis. 2007;66:222–7. doi: 10.1136/ard.2006.054593Watts R, Lane S, Hanslik T, et al. Development and validation of a consensus methodology for the classification of the ANCAassociated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis. 2007;66:222–7. doi: 10.1136/ard.2006.054593Luqmani R, Bacon P, Moots R, et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. 1994;87:671–8.Luqmani R, Bacon P, Moots R, et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. 1994;87:671–8.Schö nermarck U, Csernok E, Gross WL. Pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis: challenges and solutions 2014. Nephrol Dial Transplant. 2014(Dec 23) pii: gfu398. [Epub ahead of print]. Review. PubMed PMID: 25540095.Schö nermarck U, Csernok E, Gross WL. Pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis: challenges and solutions 2014. Nephrol Dial Transplant. 2014(Dec 23) pii: gfu398. [Epub ahead of print]. Review. PubMed PMID: 25540095.Hilhorst M, Shirai T, Berry G, et al. T cell-macrophage interactions and granuloma formation in vasculitis. Front Immunol. 2014(Sep)12;5:432.Hilhorst M, Shirai T, Berry G, et al. T cell-macrophage interactions and granuloma formation in vasculitis. Front Immunol. 2014(Sep)12;5:432.Nogueira E, Hamour S, Sawant D, et al. Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis. Nephrol Dial Transplant. 2010;25(7):2209–17. doi: 10.1093/ndt/gfp783Nogueira E, Hamour S, Sawant D, et al. Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis. Nephrol Dial Transplant. 2010;25(7):2209–17. doi: 10.1093/ndt/gfp783Schnurr M, Toy T, Shin A, et al. Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway. Blood. 2005;105:1582–9. doi: 10.1182/blood-2004-05-1718Schnurr M, Toy T, Shin A, et al. Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway. Blood. 2005;105:1582–9. doi: 10.1182/blood-2004-05-1718Torchinsky MB, Blander JM. T helper 17 cells: discovery, function,and physiological trigger. Cell Mol Life Sci. 2010(May);67(9):1407–21.Torchinsky MB, Blander JM. T helper 17 cells: discovery, function,and physiological trigger. Cell Mol Life Sci. 2010(May);67(9):1407–21.Zhou L, Lopes JE, Chong MMW, et al. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORt function. Nature. 2008;453:236–40. doi: 10.1038/nature06878Zhou L, Lopes JE, Chong MMW, et al. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORt function. Nature. 2008;453:236–40. doi: 10.1038/nature06878Tesmer LA, Lundy K, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008;223:87–113. doi: 10.1111/j.1600-065X.2008.00628.xTesmer LA, Lundy K, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008;223:87–113. doi: 10.1111/j.1600-065X.2008.00628.xKim HS, Choi D, Lim LL, et al. Association of interleukin 23 receptor gene with sarcoidosis. Dis Markers. 2011;31(1):17–24. doi: 10.1155/2011/185106Kim HS, Choi D, Lim LL, et al. Association of interleukin 23 receptor gene with sarcoidosis. Dis Markers. 2011;31(1):17–24. doi: 10.1155/2011/185106Oliver B, Rueda MA, Lopez-Nevot M, et al. Replication of an association between IL23R gene polymorphism with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007;5:977–81. doi: 10.1016/j.cgh.2007.05.002Oliver B, Rueda MA, Lopez-Nevot M, et al. Replication of an association between IL23R gene polymorphism with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007;5:977–81. doi: 10.1016/j.cgh.2007.05.002Nair RP, Duffin KC, Helms C, et al; Collaborative Association Study of Psoriasis. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009;41(2):199–204. doi: 10.1038/ng.311Nair RP, Duffin KC, Helms C, et al; Collaborative Association Study of Psoriasis. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009;41(2):199–204. doi: 10.1038/ng.311Duan Z, Pan F, Zeng Z, et al. Interleukin-23 receptor genetic polymorphisms and ankylosing spondylitis susceptibility: a metaanalysis. Rheumatol Int. 2012(May);32(5):1209–14.Duan Z, Pan F, Zeng Z, et al. Interleukin-23 receptor genetic polymorphisms and ankylosing spondylitis susceptibility: a metaanalysis. Rheumatol Int. 2012(May);32(5):1209–14.Tsai JP, Yang SF, Wu SW, et al. Association between interleukin 23 receptor polymorphism and kidney transplant outcomes: a 10-year Taiwan cohort study. Clin Chim Acta. 2011;412(11–12):958–62. doi: 10.1016/j.cca.2011.01.031Tsai JP, Yang SF, Wu SW, et al. Association between interleukin 23 receptor polymorphism and kidney transplant outcomes: a 10-year Taiwan cohort study. Clin Chim Acta. 2011;412(11–12):958–62. doi: 10.1016/j.cca.2011.01.031Paust HJ, Turner JE, Steinmetz OM, et al. The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis. J Am Soc Nephrol. 2009;20(5):969–79. doi: 10.1681/ASN.2008050556Paust HJ, Turner JE, Steinmetz OM, et al. The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis. J Am Soc Nephrol. 2009;20(5):969–79. doi: 10.1681/ASN.2008050556Gan P-Y, Steinmetz OM, Tan DSY, et al. Th17 cells promote autoimmune anti-myeloperoxidase glomerulonephritis. J Am Soc Nephrol. 2010;21:925–31. doi: 10.1681/ASN.2009070763Gan P-Y, Steinmetz OM, Tan DSY, et al. Th17 cells promote autoimmune anti-myeloperoxidase glomerulonephritis. J Am Soc Nephrol. 2010;21:925–31. doi: 10.1681/ASN.2009070763Yen D, Cheung J, Scheerens H, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006;116:1310–6. doi: 10.1172/JCI21404Yen D, Cheung J, Scheerens H, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006;116:1310–6. doi: 10.1172/JCI21404Kyttaris VC, Zhang Z, Kuchroo VK, et al. Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. J Immunol. 2010;184(9):4605–9. doi: 10.4049/jimmunol.0903595Kyttaris VC, Zhang Z, Kuchroo VK, et al. Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. J Immunol. 2010;184(9):4605–9. doi: 10.4049/jimmunol.0903595Ooi JD, Phoon RK, Holdsworth SR, Kitching AR. IL-23, not IL-12, directs autoimmunity to the Goodpasture antigen. J Am Soc Nephrol. 2009;20(5):980–9. doi: 10.1681/ASN.2008080891Ooi JD, Phoon RK, Holdsworth SR, Kitching AR. IL-23, not IL-12, directs autoimmunity to the Goodpasture antigen. J Am Soc Nephrol. 2009;20(5):980–9. doi: 10.1681/ASN.2008080891Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744–8. doi: 10.1038/nature01355Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744–8. doi: 10.1038/nature01355Murphy CA, Langrish CL, Chen Y, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003;198:1951–7. doi: 10.1084/jem.20030896Murphy CA, Langrish CL, Chen Y, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003;198:1951–7. doi: 10.1084/jem.20030896Ogawa A, Andoh A, Araki Y, et al. Neutralization of interleukin- 17 aggravates dextran sulfate sodium-induced colitis in mice. Clin Immunol. 2004;110:55–62. doi: 10.1016/j.clim.2003.09.013Ogawa A, Andoh A, Araki Y, et al. Neutralization of interleukin- 17 aggravates dextran sulfate sodium-induced colitis in mice. Clin Immunol. 2004;110:55–62. doi: 10.1016/j.clim.2003.09.013Becker C, Dornhoff H, Neufert C, et al. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J Immunol. 2006;177(5):2760–4. doi: 10.4049/jimmunol.177.5.2760Becker C, Dornhoff H, Neufert C, et al. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J Immunol. 2006;177(5):2760–4. doi: 10.4049/jimmunol.177.5.2760Savvatis K, Pappritz K, Becher PM, et al. Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction. Circ Heart Fail. 2014;7(1):161–71. doi: 10.1161/CIRCHEARTFAILURE.113.000604Savvatis K, Pappritz K, Becher PM, et al. Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction. Circ Heart Fail. 2014;7(1):161–71. doi: 10.1161/CIRCHEARTFAILURE.113.000604Olewicz-Gawlik A, Danczak-Pazdrowska A, Kuznar-Kaminska B, et al. Interleukin-17 and interleukin-23: importance in the pathogenesis of lung impairment in patients with systemic sclerosis. Int J Rheum Dis. 2014;17(6):664–70. doi: 10.1111/1756- 185X.12290Olewicz-Gawlik A, Danczak-Pazdrowska A, Kuznar-Kaminska B, et al. Interleukin-17 and interleukin-23: importance in the pathogenesis of lung impairment in patients with systemic sclerosis. Int J Rheum Dis. 2014;17(6):664–70. doi: 10.1111/1756- 185X.12290Masaki K, Suzuki Y, Kagawa S, et al. Dual role of interleukin-23 in epicutaneously-sensitized asthma in mice. Allergol Int. 2014;63(Suppl 1):13–22. doi: 10.2332/allergolint.13-OA-0632Masaki K, Suzuki Y, Kagawa S, et al. Dual role of interleukin-23 in epicutaneously-sensitized asthma in mice. Allergol Int. 2014;63(Suppl 1):13–22. doi: 10.2332/allergolint.13-OA-0632Harrington LE, Hatton RD, Mangan PR. Interleukin 17-producing CD4+ effector T cells develop via a lineage dis-tinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–32. doi: 10.1038/ni1254Harrington LE, Hatton RD, Mangan PR. Interleukin 17-producing CD4+ effector T cells develop via a lineage dis-tinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–32. doi: 10.1038/ni1254Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41. doi: 10.1038/ni1261Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41. doi: 10.1038/ni1261Afzali B, Lombardi G, Lecher RI, Lord GM. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exper Immunol. 2007;148:32–46. doi: 10.1111/j.1365-2249.2007.03356.xAfzali B, Lombardi G, Lecher RI, Lord GM. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exper Immunol. 2007;148:32–46. doi: 10.1111/j.1365-2249.2007.03356.xKasper LH, Everitt D, Leist TP, et al. A phase I trial of an interleukin-12/23 monoclonal antibody in relapsing multiple sclerosis. Curr Med Res Opin. 2006;22:1671–8. doi: 10.1185/030079906X120931Kasper LH, Everitt D, Leist TP, et al. A phase I trial of an interleukin-12/23 monoclonal antibody in relapsing multiple sclerosis. Curr Med Res Opin. 2006;22:1671–8. doi: 10.1185/030079906X120931McGeachy MJ, Bak-Jensen KS, Chen Y, et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol. 2007;8:1390–7. doi: 10.1038/ni1539McGeachy MJ, Bak-Jensen KS, Chen Y, et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol. 2007;8:1390–7. doi: 10.1038/ni1539Fitzgerald DC, Ciric B, Touil T, et al. Suppressive effect of IL-27 on encephalolithogenic TH17 cells and the effector phase of experimental autoimmune encephalomyelitis. J Immunol. 2007;179:3268–327. doi: 10.4049/jimmunol.179.5.3268Fitzgerald DC, Ciric B, Touil T, et al. Suppressive effect of IL-27 on encephalolithogenic TH17 cells and the effector phase of experimental autoimmune encephalomyelitis. J Immunol. 2007;179:3268–327. doi: 10.4049/jimmunol.179.5.3268Velden J, Paust HJ, Hoxha E, et al. Renal IL-17 expression in human ANCA-associated glomerulonephritis. Am J Physiol Renal Physiol. 2012;302(12):1663–73. doi: 10.1152/ajprenal.00683.2011Velden J, Paust HJ, Hoxha E, et al. Renal IL-17 expression in human ANCA-associated glomerulonephritis. Am J Physiol Renal Physiol. 2012;302(12):1663–73. doi: 10.1152/ajprenal.00683.2011Stummvoll GH, DiPaolo TS, Glass D, et al. Th1, Th2 and Th17 effector T cell-induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells. J Immunol. 2008;181:1908–16. doi: 10.4049/jimmunol. 181.3.1908Stummvoll GH, DiPaolo TS, Glass D, et al. Th1, Th2 and Th17 effector T cell-induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells. J Immunol. 2008;181:1908–16. doi: 10.4049/jimmunol. 181.3.1908Yu JJ, Gaffen SL. Interleukin-17: a novel inflammatory cytokine that bridges innate and adaptive immunity. Front Biosci. 2008;13:170–7. doi: 10.2741/2667Yu JJ, Gaffen SL. Interleukin-17: a novel inflammatory cytokine that bridges innate and adaptive immunity. Front Biosci. 2008;13:170–7. doi: 10.2741/2667Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. J Immunity. 2008;28:454–67. doi: 10.1016/j.immuni.2008.03.004Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. J Immunity. 2008;28:454–67. doi: 10.1016/j.immuni.2008.03.004Happel KI, Zheng M, Young E, et al. Cutting edge: roles of Tolllike receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection. J Immunol. 2003;170(9):4432–6. doi: 10.4049/jimmunol.170.9.4432Happel KI, Zheng M, Young E, et al. Cutting edge: roles of Tolllike receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection. J Immunol. 2003;170(9):4432–6. doi: 10.4049/jimmunol.170.9.4432Aujla SJ, Chan YR, Zheng M, et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med. 2008;14(3):275–81. doi: 10.1038/nm1710Aujla SJ, Chan YR, Zheng M, et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med. 2008;14(3):275–81. doi: 10.1038/nm1710Huang W, Na L, Fidel PL, Schwarzenberger P. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis. 2004;190:624–31. doi: 10.1086/422329Huang W, Na L, Fidel PL, Schwarzenberger P. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis. 2004;190:624–31. doi: 10.1086/422329Kelly MN, Kolls JK, Happel K, et al. Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection. Infect Immun. 2005;73(1):617–21. doi: 10.1128/IAI.73.1.617-621.2005Kelly MN, Kolls JK, Happel K, et al. Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection. Infect Immun. 2005;73(1):617–21. doi: 10.1128/IAI.73.1.617-621.2005Weaver CT, Hatton RD, Hangan PR, Harringon LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Ann Rev Immunol. 2007;25:821–52. doi: 10.1146/annurev.immunol.25.022106.141557Weaver CT, Hatton RD, Hangan PR, Harringon LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Ann Rev Immunol. 2007;25:821–52. doi: 10.1146/annurev.immunol.25.022106.141557Wilde B, Thewissen M, Damoiseaux J, et al. Th17 expansion in granulomatosis with polyangiitis (Wegener’s): the role of disease activity, immune regulation and therapy. Arthritis Res Ther. 2012;14(5):R227. doi: 10.1186/ar4066Wilde B, Thewissen M, Damoiseaux J, et al. Th17 expansion in granulomatosis with polyangiitis (Wegener’s): the role of disease activity, immune regulation and therapy. Arthritis Res Ther. 2012;14(5):R227. doi: 10.1186/ar4066Fagin U, Csernok E, Muller A, et al. Distinct proteinase 3-induced cytokine patterns in Wegener’s granulomatosis, Churg-Strauss syndrome, and healthy controls. Clin Exp Rheumatol. 2011;29:57–62.Fagin U, Csernok E, Muller A, et al. Distinct proteinase 3-induced cytokine patterns in Wegener’s granulomatosis, Churg-Strauss syndrome, and healthy controls. Clin Exp Rheumatol. 2011;29:57–62.Abdulahad WH, Stegeman CA, Limburg PC, Kallenberg CG. Skewed distribution of Th17 lymphocytes in patients with Wegener's granulomatosis in remission. Arthritis Rheum. 2008;58(7):2196–205. doi: 10.1002/art.23557Abdulahad WH, Stegeman CA, Limburg PC, Kallenberg CG. Skewed distribution of Th17 lymphocytes in patients with Wegener's granulomatosis in remission. Arthritis Rheum. 2008;58(7):2196–205. doi: 10.1002/art.23557Мазуров ВИ, Долгих СВ. Диагностическая значимость биологических маркеров при первичных системных некротизирующих васкулитах. Вестник Санкт- Петербургской медицинской академии последипломного образования. 2010;1(2):4–8 [Mazurov VI, Dolgikh SV. The diagnostic value of biomarkers in primary systemic necrotizing vasculitis. Vestnik Sankt-Peterburgskoi meditsinskoi akademii poslediplomnogo obrazovaniya. 2010;1(2):4–8 (In Russ.)].Мазуров ВИ, Долгих СВ. Диагностическая значимость биологических маркеров при первичных системных некротизирующих васкулитах. Вестник Санкт- Петербургской медицинской академии последипломного образования. 2010;1(2):4–8 [Mazurov VI, Dolgikh SV. The diagnostic value of biomarkers in primary systemic necrotizing vasculitis. Vestnik Sankt-Peterburgskoi meditsinskoi akademii poslediplomnogo obrazovaniya. 2010;1(2):4–8 (In Russ.)].Hemdan NY, Birkenmeier G, Wichmann G, et al. Interleukin-17-producing T helper cells in autoimmunity. Autoimmun Rev. 2010;9(11):785–92. doi: 10.1016/j.autrev.2010.07.003Hemdan NY, Birkenmeier G, Wichmann G, et al. Interleukin-17-producing T helper cells in autoimmunity. Autoimmun Rev. 2010;9(11):785–92. doi: 10.1016/j.autrev.2010.07.003Deng J, Younge BR, Olshen RA, et al. Th17 and Th1 T-Cell responses in giant cell arteritis. Circulation. 2010;121:906–15. doi: 10.1161/CIRCULATIONAHA.109.872903Deng J, Younge BR, Olshen RA, et al. Th17 and Th1 T-Cell responses in giant cell arteritis. Circulation. 2010;121:906–15. doi: 10.1161/CIRCULATIONAHA.109.872903Miossec P. Interleukin-17 and Th17 cells: From adult to juvenile arthritis – now it is serious! Arthritis Rheum. 2011;63:2168–71. doi: 10.1002/art.30331Miossec P. Interleukin-17 and Th17 cells: From adult to juvenile arthritis – now it is serious! Arthritis Rheum. 2011;63:2168–71. doi: 10.1002/art.30331Von Vietinghoff S, Ley K. Interleukin 17 in vascular inflammation. Cytokine Growth Factor Rev. 2010;21:463–9. doi: 10.1016/j.cytogfr.2010.10.003Von Vietinghoff S, Ley K. Interleukin 17 in vascular inflammation. Cytokine Growth Factor Rev. 2010;21:463–9. doi: 10.1016/j.cytogfr.2010.10.003Yang J, Chu Y, Yang X, et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum. 2009;60:1472–83. doi: 10.1002/art.24499Yang J, Chu Y, Yang X, et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum. 2009;60:1472–83. doi: 10.1002/art.24499Brentano F, Ospelt C, Stanczyk J, et al. Abundant expression of the interleukin (IL) 23 subunit p19, but low levels of bioactive IL23 in the rheumatoid synovium: Differential expression and Toll-like receptor-(TLR) dependent regulation of the IL23 subunits, p19 and p40, in rheumatoid arthritis. Ann Rheum Dis. 2009;68(1):143–50. doi: 10.1136/ard.2007.082081Brentano F, Ospelt C, Stanczyk J, et al. Abundant expression of the interleukin (IL) 23 subunit p19, but low levels of bioactive IL23 in the rheumatoid synovium: Differential expression and Toll-like receptor-(TLR) dependent regulation of the IL23 subunits, p19 and p40, in rheumatoid arthritis. Ann Rheum Dis. 2009;68(1):143–50. doi: 10.1136/ard.2007.082081Chabaud M, Lubberts E, Joosten L, et al. IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. Arthritis Res. 2001;3:168–77. doi: 10.1186/ar294Chabaud M, Lubberts E, Joosten L, et al. IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. Arthritis Res. 2001;3:168–77. doi: 10.1186/ar294Dalila AS, Mohd Said MS, Shaharir SS, et al. Interleukin-23 and its correlation with disease activity, joint damage, and functional disability in rheumatoid arthritis. Kaohsiung J Med Sci. 2014;30(7):337–42. doi: 10.1016/j.kjms.2014.02.010Dalila AS, Mohd Said MS, Shaharir SS, et al. Interleukin-23 and its correlation with disease activity, joint damage, and functional disability in rheumatoid arthritis. Kaohsiung J Med Sci. 2014;30(7):337–42. doi: 10.1016/j.kjms.2014.02.010Wang X, Lin Z, Wei Q, et al. Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis. Rheumatol Int. 2009;29(11):1343–7. doi: 10.1007/s00296-009- 0883-xWang X, Lin Z, Wei Q, et al. Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis. Rheumatol Int. 2009;29(11):1343–7. doi: 10.1007/s00296-009- 0883-xMei Y, Pan F, Gao J, et al. Increased serum IL-17 and IL-23 in the patient with ankylosing spondylitis. Clin Rheumatol. 2011;30(2):269–73. doi: 10.1007/s10067-010-1647-4Mei Y, Pan F, Gao J, et al. Increased serum IL-17 and IL-23 in the patient with ankylosing spondylitis. Clin Rheumatol. 2011;30(2):269–73. doi: 10.1007/s10067-010-1647-4Chen WS, Chang YS, Lin KC, et al. Association of serum interleukin-17 and interleukin-23 levels with disease activity in Chinese patients with ankylosing spondylitis. J Chin Med Assoc. 2012;75(7):303–8. doi: 10.1016/j.jcma.2012.05.006Chen WS, Chang YS, Lin KC, et al. Association of serum interleukin-17 and interleukin-23 levels with disease activity in Chinese patients with ankylosing spondylitis. J Chin Med Assoc. 2012;75(7):303–8. doi: 10.1016/j.jcma.2012.05.006Gheita TA, El Gazzar II, El-Fishawy HS, et al. Involvement of IL-23 in enteropathic arthritis patients with inflammatory bowel disease: preliminary results. Clin Rheumatol. 2014;33(5):713–7. doi: 10.1007/s10067-013-2469-yGheita TA, El Gazzar II, El-Fishawy HS, et al. Involvement of IL-23 in enteropathic arthritis patients with inflammatory bowel disease: preliminary results. Clin Rheumatol. 2014;33(5):713–7. doi: 10.1007/s10067-013-2469-ySaadoun D, Garrido M, Comarmond C, et al. Th1 and Th17 cytokines drive Takayasu Arteritis inflammation. Arthritis Rheum. 2015 Jan 20. doi: 10.1002/art.39037 [Epub ahead of print].Saadoun D, Garrido M, Comarmond C, et al. Th1 and Th17 cytokines drive Takayasu Arteritis inflammation. Arthritis Rheum. 2015 Jan 20. doi: 10.1002/art.39037 [Epub ahead of print].Weyand CM, Younge BR, Goronzy JJ. IFN-γ and IL-17: the two faces of T-cell pathology in giant cell arteritis. Curr Opin Rheumatol. 2011;23(1):43–9. doi: 10.1097/BOR.0b013e32833ee946Weyand CM, Younge BR, Goronzy JJ. IFN-γ and IL-17: the two faces of T-cell pathology in giant cell arteritis. Curr Opin Rheumatol. 2011;23(1):43–9. doi: 10.1097/BOR.0b013e32833ee946Xia L, Li B, Shen H, Lu J. Interleukin-27 and interleukin-23 in patients with systemic lupus erythematosus: possible role in lupus nephritis. Scand J Rheumatol. 2015;6:1–6. doi: 10.3109/03009742.2014.962080Xia L, Li B, Shen H, Lu J. Interleukin-27 and interleukin-23 in patients with systemic lupus erythematosus: possible role in lupus nephritis. Scand J Rheumatol. 2015;6:1–6. doi: 10.3109/03009742.2014.962080Huang X, Hua J, Shen N, et al. Dysregulated expression of interleukin-23 and interleukin-12 subunits in systemic lupus erythematosus patients. Mod Rheumatol. 2007;17:220–3. doi: 10.3109/s10165-007-0568-9Huang X, Hua J, Shen N, et al. Dysregulated expression of interleukin-23 and interleukin-12 subunits in systemic lupus erythematosus patients. Mod Rheumatol. 2007;17:220–3. doi: 10.3109/s10165-007-0568-9Puwipirom H, Hirankarn N, Sodsai P, et al. Increased interleukin-23 receptor(+) T cells in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Arthritis Res Ther. 2010;12:215. doi: 10.1186/ar3194Puwipirom H, Hirankarn N, Sodsai P, et al. Increased interleukin-23 receptor(+) T cells in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Arthritis Res Ther. 2010;12:215. doi: 10.1186/ar3194Ruggeri RM, Saitta S, Cristani M, et al. Serum interleukin-23 (IL-23) is increased in Hashimoto’s thyroiditis. Endocr J. 2014;61(4):359–63. doi: 10.1507/endocrj.EJ13-0484Ruggeri RM, Saitta S, Cristani M, et al. Serum interleukin-23 (IL-23) is increased in Hashimoto’s thyroiditis. Endocr J. 2014;61(4):359–63. doi: 10.1507/endocrj.EJ13-0484Chen JM, Jiang GX, Li QW, et al. Increased serum levels of interleukin-18, -23 and -17 in chinese patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2014;38(5–6):321–9. doi: 10.1159/000360606Chen JM, Jiang GX, Li QW, et al. Increased serum levels of interleukin-18, -23 and -17 in chinese patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2014;38(5–6):321–9. doi: 10.1159/000360606Vaccaro M, Cannavo SP, Imbesi S, et al. Increased serum levels of interleukin-23 circulating in patients with non-segmental generalized vitiligo. Int J Dermatol. 2014 Nov 27. doi: 10.1111/ijd.12392 [Epub ahead of print].Vaccaro M, Cannavo SP, Imbesi S, et al. Increased serum levels of interleukin-23 circulating in patients with non-segmental generalized vitiligo. Int J Dermatol. 2014 Nov 27. doi: 10.1111/ijd.12392 [Epub ahead of print].Leonardi S, Cuppari C, Manti S, et al. Serum interleukin 17, interleukin 23, and interleukin 10 values in children with atopic eczema/dermatitis syndrome (AEDS): Association with clinical severity and phenotype. Allergy Asthma Proc. 2015;36(1):74–81. doi: 10.2500/aap.2015.36.3808Leonardi S, Cuppari C, Manti S, et al. Serum interleukin 17, interleukin 23, and interleukin 10 values in children with atopic eczema/dermatitis syndrome (AEDS): Association with clinical severity and phenotype. Allergy Asthma Proc. 2015;36(1):74–81. doi: 10.2500/aap.2015.36.3808Yu C, Gong X, Yang Q, et al. The serum IL-23 level predicts the response to pegylated interferon therapy in patients with chronic hepatitis B. Liver Int. 2014 Oct 14; doi: 10.1111/liv.12701 [Epub ahead of print].Yu C, Gong X, Yang Q, et al. The serum IL-23 level predicts the response to pegylated interferon therapy in patients with chronic hepatitis B. Liver Int. 2014 Oct 14; doi: 10.1111/liv.12701 [Epub ahead of print].Ashrafi Hafez A, Ahmadi Vasmehjani A, Baharlou R, et al. Analytical assessment of interleukin-23 and -27 cytokines in healthy people and patients with hepatitis C virus infection (genotypes 1 and 3a). Hepat Mon. 2014 Sep 27;14(9):e21000. doi: 10.5812/hepatmon.21000Ashrafi Hafez A, Ahmadi Vasmehjani A, Baharlou R, et al. Analytical assessment of interleukin-23 and -27 cytokines in healthy people and patients with hepatitis C virus infection (genotypes 1 and 3a). Hepat Mon. 2014 Sep 27;14(9):e21000. doi: 10.5812/hepatmon.21000Jia R, Tang M, Qiu L, et al. Increased Interleukin-23/17 Axis and C-reactive protein are associated with severity of acute pancreatitis in patients. Pancreas. 2015;44(2):321–5. doi: 10.1097/MPA.0000000000000284Jia R, Tang M, Qiu L, et al. Increased Interleukin-23/17 Axis and C-reactive protein are associated with severity of acute pancreatitis in patients. Pancreas. 2015;44(2):321–5. doi: 10.1097/MPA.0000000000000284Wong CK, Lit LC, 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;127:385–93. doi: 10.1016/j.clim.2008.01.019Wong CK, Lit LC, 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;127:385–93. doi: 10.1016/j.clim.2008.01.019Alibaz-Oner F, Yentü r SP, Saruhan-Direskeneli G, Direskeneli H. Serum cytokine profiles in Takayasu’s arteritis: search for biomarkers. Clin Exp Rheumatol. 2014 Dec 1 [Epub ahead of print] PubMed PMID: 25436391.Alibaz-Oner F, Yentü r SP, Saruhan-Direskeneli G, Direskeneli H. Serum cytokine profiles in Takayasu’s arteritis: search for biomarkers. Clin Exp Rheumatol. 2014 Dec 1 [Epub ahead of print] PubMed PMID: 25436391.Du J, Li Z, Shi J, Bi L. Associations between serum interleukin-23 levels and clinical characteristics in patients with systemic lupus erythematosus. J Int Med Res. 2014;42(5):1123–30. doi: 10.1177/0300060513509130Du J, Li Z, Shi J, Bi L. Associations between serum interleukin-23 levels and clinical characteristics in patients with systemic lupus erythematosus. J Int Med Res. 2014;42(5):1123–30. doi: 10.1177/0300060513509130Wilde B, Thewissen M, Damoiseaux J, et al. Th17 expansion in granulomatosis with polyangiitis (Wegener’s): the role of disease activity, immune regulation and therapy. Arthritis Res Ther. 2012;14(5):R227. doi: 10.1186/ar4066Wilde B, Thewissen M, Damoiseaux J, et al. Th17 expansion in granulomatosis with polyangiitis (Wegener’s): the role of disease activity, immune regulation and therapy. Arthritis Res Ther. 2012;14(5):R227. doi: 10.1186/ar4066

The authors declare that there are no conflicts of interest present.