Top

Clinical Reviews in Allergy & Immunology

Published in:

Open Access 01-12-2018

The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis

Authors: Andrew Blauvelt, Andrea Chiricozzi

Published in: Clinical Reviews in Allergy & Immunology | Issue 3/2018

Abstract

Psoriasis is a chronic, immune-mediated, inflammatory disease that is pathogenically driven by proinflammatory cytokines. This article reviews the immunologic role of interleukin (IL)-17, the major effector cytokine in the pathogenesis of psoriatic disease, along with the rationale for targeting the IL-17 cytokine family (IL-17A, IL-17F, and IL-17 receptor A) in the treatment of psoriasis and psoriatic arthritis. Emerging evidence indicates that major sources of IL-17A in patients with psoriatic disease are mast cells, γδ T cells, αβ T cells, and innate lymphoid cells in lesional skin and synovial fluid. Within the skin and joints, IL-17A acts on cellular targets, including keratinocytes, neutrophils, endothelial cells, fibroblasts, osteoclasts, chondrocytes, and osteoblasts, to stimulate production of various antimicrobial peptides, chemokines, and proinflammatory and proliferative cytokines, which, in turn, promote tissue inflammation and bone remodeling. The critical importance of the IL-23/IL-17A axis to the pathogenesis of psoriatic disease has resulted in many new biologic treatments targeting these cytokines. These biologics dramatically improve skin and joint symptoms in patients with moderate-to-severe psoriasis and psoriatic arthritis.

Lowes MA, Suárez-Fariñas M, Krueger JG (2014) Immunology of psoriasis. Annu Rev Immunol 32:227–255. https://doi.org/10.1146/annurev-immunol-032713-120225 CrossRefPubMedPubMedCentral

Nestle FO, Kaplan DH, Barker J (2009) Psoriasis. N Engl J Med 361:496–509. https://doi.org/10.1056/NEJMra0804595 CrossRefPubMed

Boehncke WH, Schön MP (2015) Psoriasis. Lancet 386:983–994. https://doi.org/10.1016/S0140-6736(14)61909-7 CrossRefPubMed

Chandra A, Ray A, Senapati S, Chatterjee R (2015) Genetic and epigenetic basis of psoriasis pathogenesis. Mol Immunol 64:313–323. https://doi.org/10.1016/j.molimm.2014.12.014 CrossRefPubMed

Chiricozzi A, Guttman-Yassky E, Suárez-Fariñas M, Nograles KE, Tian S, Cardinale I, Chimenti S, Krueger JG (2011) Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol 131:677–687CrossRefPubMed

Martin DA, Towne JE, Kricorian G, Klekotka P, Gudjonsson JE, Krueger JG, Russell CB (2013) The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol 133:17–26. https://doi.org/10.1038/jid.2012.194 CrossRefPubMed

Marinoni B, Ceribelli A, Massarotti MS, Selmi C (2014) The Th17 axis in psoriatic disease: pathogenetic and therapeutic implications. Auto Immun Highlights 5:9–19. https://doi.org/10.1007/s13317-013-0057-4 CrossRefPubMedPubMedCentral

Chiricozzi A, Suárez-Fariñas M, Fuentes-Duculan J, Cueto I, Li K, Tian S, Brodmerkel C, Krueger JG (2016) Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris. Br J Dermatol 174:136–145. https://doi.org/10.1111/bjd.14034 CrossRefPubMed

Wang CQ, Suarez-Farinas M, Nograles KE, Mimoso CA, Shrom D, Dow ER, Heffernan MP, Hoffman RW, Krueger JG (2014) IL-17 induces inflammation-associated gene products in blood monocytes, and treatment with ixekizumab reduces their expression in psoriasis patient blood. J Invest Dermatol 134:2990–2993. https://doi.org/10.1038/jid.2014.268 CrossRefPubMed

10.

Kirkham BW, Kavanaugh A, Reich K (2014) Interleukin-17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis. Immunology 141:133–142. https://doi.org/10.1111/imm.12142 CrossRefPubMedPubMedCentral

11.

Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A (2010) Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol 130:1373–1383. https://doi.org/10.1038/jid.2009.399 CrossRefPubMed

12.

Belasco J, Louie JS, Gulati N, Wei N, Nograles K, Fuentes-Duculan J, Mitsui H, Suárez-Fariñas M, Krueger JG (2015) Comparative genomic profiling of synovium versus skin lesions in psoriatic arthritis. Arthritis Rheumatol 67:934–944. https://doi.org/10.1002/art.38995 CrossRefPubMedPubMedCentral

13.

Chiricozzi A, Nograles KE, Johnson-Huang LM, Fuentes-Duculan J, Cardinale I, Bonifacio KM, Gulati N, Mitsui H, Guttman-Yassky E, Suárez-Fariñas M, Krueger JG (2014) IL-17 induces an expanded range of downstream genes in reconstituted human epidermis model. PLoS One 9:e90284. https://doi.org/10.1371/journal.pone.0090284 CrossRefPubMedPubMedCentral

14.

Lande R, Botti E, Jandus C, Dojcinovic D, Fanelli G, Conrad C, Chamilos G, Feldmeyer L, Marinari B, Chon S, Vence L, Riccieri V, Guillaume P, Navarini AA, Romero P, Costanzo A, Piccolella E, Gilliet M, Frasca L (2014) The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun 5:5621. https://doi.org/10.1038/ncomms6621 CrossRefPubMed

15.

Krueger JG (2015) An autoimmune “attack” on melanocytes triggers psoriasis and cellular hyperplasia. J Exp Med 212:2186. https://doi.org/10.1084/jem.21213insight3 CrossRefPubMedPubMedCentral

16.

Arakawa A, Siewert K, Stöhr J, Besgen P, Kim SM, Rühl G, Nickel J, Vollmer S, Thomas P, Krebs S, Pinkert S, Spannagl M, Held K, Kammerbauer C, Besch R, Dornmair K, Prinz JC (2015) Melanocyte antigen triggers autoimmunity in human psoriasis. J Exp Med 212:2203–2212. https://doi.org/10.1084/jem.20151093 CrossRefPubMedPubMedCentral

17.

Gaffen SL (2011) Recent advances in the IL-17 cytokine family. Curr Opin Immunol 23:613–619. https://doi.org/10.1016/j.coi.2011.07.006 CrossRefPubMedPubMedCentral

18.

Hymowitz SG, Filvaroff EH, Yin JP, Lee J, Cai L, Risser P, Maruoka M, Mao W, Foster J, Kelley RF, Pan G, Gurney AL, de Vos AM, Starovasnik MA (2001) IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding. EMBO J 20:5332–5341. https://doi.org/10.1093/emboj/20.19.5332 CrossRefPubMedPubMedCentral

19.

Li H, Chen J, Huang A, Stinson J, Heldens S, Foster J, Dowd P, Gurney AL, Wood WI (2000) Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family. Proc Natl Acad Sci U S A 97:773–778CrossRefPubMedPubMedCentral

20.

Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, Menon S, Clifford T, Hunte B, Lesley R, Muchamuel T, Hurst SD, Zurawski G, Leach MW, Gorman DM, Rennick DM (2001) IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15:985–995CrossRefPubMed

21.

Starnes T, Broxmeyer HE, Robertson MJ, Hromas R (2002) Cutting edge: IL-17D, a novel member of the IL-17 family, stimulates cytokine production and inhibits hemopoiesis. J Immunol 169:642–646CrossRefPubMed

22.

Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, Dong C (2008) Regulation of inflammatory responses by IL-17F. J Exp Med 205:1063–1075. https://doi.org/10.1084/jem.20071978 CrossRefPubMedPubMedCentral

23.

Chang SH, Reynolds JM, Pappu BP, Chen G, Martinez GJ, Dong C (2011) Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. Immunity 35:611–621. https://doi.org/10.1016/j.immuni.2011.09.010 CrossRefPubMedPubMedCentral

24.

Johansen C, Usher PA, Kjellerup RB, Lundsgaard D, Iversen L, Kragballe K (2009) Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol 160:319–324. https://doi.org/10.1111/j.1365-2133.2008.08902.x CrossRefPubMed

25.

Johnston A, Fritz Y, Dawes SM, Diaconu D, Al-Attar PM, Guzman AM, Chen CS, Fu W, Gudjonsson JE, McCormick TS, Ward NL (2013) Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J Immunol 190:2252–2262. https://doi.org/10.4049/jimmunol.1201505 CrossRefPubMed

26.

Muromoto R, Hirao T, Tawa K, Hirashima K, Kon S, Kitai Y, Matsuda T (2016) IL-17A plays a central role in the expression of psoriasis signature genes through the induction of IκB-ζ in keratinocytes. Int Immunol 28:443–452. https://doi.org/10.1093/intimm/dxw011 CrossRefPubMed

27.

Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, Puig L, Nakagawa H, Spelman L, Sigurgeirsson B, Rivas E, Tsai TF, Wasel N, Tyring S, Salko T, Hampele I, Notter M, Karpov A, Helou S, Papavassilis C, ERASURE and FIXTURE Study Groups (2014) Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med 371:326–338. https://doi.org/10.1056/NEJMoa1314258 CrossRefPubMed

28.

Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, Reich K, Amato D, Ball SG, Braun DK, Cameron GS, Erickson J, Konrad RJ, Muram TM, Nickoloff BJ, Osuntokun OO, Secrest RJ, Zhao F, Mallbris L, Leonardi CL, UNCOVER-1, UNCOVER-2, UNCOVER-3 Study Groups (2016) Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med 375:345–356. https://doi.org/10.1056/NEJMoa1512711 CrossRefPubMed

29.

Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH, Psoriasis Study G, Durez P, Tak PP, Gomez-Reino JJ, Rheumatoid Arthritis Study G, Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD, Uveitis Study G, Rose K, Haider A, Di Padova F (2010) Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2:52ra72. https://doi.org/10.1126/scitranslmed.3001107 CrossRefPubMed

30.

Krueger JG, Fretzin S, Suárez-Fariñas M, Haslett PA, Phipps KM, Cameron GS, McColm J, Katcherian A, Cueto I, White T, Banerjee S, Hoffman RW (2012) IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol 130:145–154CrossRefPubMedPubMedCentral

31.

Zaba LC, Suárez-Fariñas M, Fuentes-Duculan J, Nograles KE, Guttman-Yassky E, Cardinale I, Lowes MA, Krueger JG (2009) Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes. J Allergy Clin Immunol 124:1022-10.e1–1022-10395. https://doi.org/10.1016/j.jaci.2009.08.046 CrossRef

32.

Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupe P, Barillot E, Soumelis V (2008) A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human T_H-17 responses. Nat Immunol 9:650–657. https://doi.org/10.1038/ni.1613 CrossRefPubMed

33.

Wei L, Laurence A, Elias KM, O'Shea JJ (2007) IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem 282:34605–34610. https://doi.org/10.1074/jbc.M705100200 CrossRefPubMed

34.

Di Cesare A, Di Meglio P, Nestle FO (2009) The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol 129:1339–1350. https://doi.org/10.1038/jid.2009.59 CrossRefPubMed

35.

Stritesky GL, Yeh N, Kaplan MH (2008) IL-23 promotes maintenance but not commitment to the Th17 lineage. J Immunol 181:5948–5955CrossRefPubMed

36.

Mortezavi M, Ritchlin C (2015) Immunologic advances reveal new targets in psoriasis and psoriatic arthritis. Discov Med 20:169–175PubMed

37.

Benham H, Norris P, Goodall J, Wechalekar MD, FitzGerald O, Szentpetery A, Smith M, Thomas R, Gaston H (2013) Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis Res Ther 15:R136. https://doi.org/10.1186/ar4317 CrossRefPubMedPubMedCentral

38.

Raychaudhuri SP, Raychaudhuri SK (2017) Mechanistic rationales for targeting interleukin-17A in spondyloarthritis. Arthritis Res Ther 19:51. https://doi.org/10.1186/s13075-017-1249-5 CrossRefPubMedPubMedCentral

39.

Ueyama A, Imura C, Fusamae Y, Tsujii K, Furue Y, Aoki M, Suzuki M, Okuda T, Oshima I, Yasui K, Shichijo M, Yamamoto M (2017) Potential role of IL-17-producing CD4/CD8 double negative αβ T cells in psoriatic skin inflammation in a TPA-induced STAT3C transgenic mouse model. J Dermatol Sci 85:27–35. https://doi.org/10.1016/j.jdermsci.2016.10.007 CrossRefPubMed

40.

Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S, Villanueva EC, Shah P, Kaplan MJ, Bruce AT (2011) Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol 187:490–500. https://doi.org/10.4049/jimmunol.1100123 CrossRefPubMed

41.

Keijsers RR, Hendriks AG, van Erp PE, van Cranenbroek B, van de Kerkhof PC, Koenen HJ, Joosten I (2014) In vivo induction of cutaneous inflammation results in the accumulation of extracellular trap-forming neutrophils expressing RORγt and IL-17. J Invest Dermatol 134:1276–1284. https://doi.org/10.1038/jid.2013.526 CrossRefPubMed

42.

Mashiko S, Bouguermouh S, Rubio M, Baba N, Bissonnette R, Sarfati M (2015) Human mast cells are major IL-22 producers in patients with psoriasis and atopic dermatitis. J Allergy Clin Immunol 136:351–359 e351. https://doi.org/10.1016/j.jaci.2015.01.033 CrossRefPubMed

43.

Leijten EF, van Kempen TS, Boes M, Michels-van Amelsfort JM, Hijnen D, Hartgring SA, van Roon JA, Wenink MH, Radstake TR (2015) Brief report: enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid. Arthritis Rheumatol 67:2673–2678. https://doi.org/10.1002/art.39261 CrossRefPubMed

44.

Dyring-Andersen B, Geisler C, Agerbeck C, Lauritsen JP, Gúdjonsdottir SD, Skov L, Bonefeld CM (2014) Increased number and frequency of group 3 innate lymphoid cells in nonlesional psoriatic skin. Br J Dermatol 170:609–616. https://doi.org/10.1111/bjd.12658 CrossRefPubMed

45.

Villanova F, Flutter B, Tosi I, Grys K, Sreeneebus H, Perera GK, Chapman A, Smith CH, Di Meglio P, Nestle FO (2014) Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis. J Invest Dermatol 134:984–991. https://doi.org/10.1038/jid.2013.477 CrossRefPubMed

46.

Bystrom J, Taher TE, Muhyaddin MS, Clanchy FI, Mangat P, Jawad AS, Williams RO, Mageed RA (2015) Harnessing the therapeutic potential of Th17 cells. Mediat Inflamm 2015:205156–205111. https://doi.org/10.1155/2015/205156 CrossRef

47.

Keijsers RR, Joosten I, van Erp PE, Koenen HJ, van de Kerkhof PC (2014) Cellular sources of IL-17 in psoriasis: a paradigm shift? Exp Dermatol 23:799–803. https://doi.org/10.1111/exd.12487 CrossRefPubMed

48.

Reich K, Papp KA, Matheson RT, Tu JH, Bissonnette R, Bourcier M, Gratton D, Kunynetz RA, Poulin Y, Rosoph LA, Stingl G, Bauer WM, Salter JM, Falk TM, Blödorn-Schlicht NA, Hueber W, Sommer U, Schumacher MM, Peters T, Kriehuber E, Lee DM, Wieczorek GA, Kolbinger F, Bleul CC (2015) Evidence that a neutrophil-keratinocyte crosstalk is an early target of IL-17A inhibition in psoriasis. Exp Dermatol 24:529–535. https://doi.org/10.1111/exd.12710 CrossRefPubMedPubMedCentral

49.

Tamarozzi F, Wright HL, Thomas HB, Edwards SW, Taylor MJ (2014) A lack of confirmation with alternative assays questions the validity of IL-17A expression in human neutrophils using immunohistochemistry. Immunol Lett 162:194–198. https://doi.org/10.1016/j.imlet.2014.10.025 CrossRefPubMed

50.

Tamassia N, Arruda-Silva F, Calzetti F, Lonardi S, Gasperini S, Gardiman E, Bianchetto-Aguilera F, Gatta LB, Girolomoni G, Mantovani A, Vermi W, Cassatella MA (2018) A reappraisal on the potential ability of human neutrophils to express and produce IL-17 family members in vitro: failure to reproducibly detect it. Front Immunol 9:795. https://doi.org/10.3389/fimmu.2018.00795 CrossRefPubMedPubMedCentral

51.

Tamassia N, Bianchetto-Aguilera F, Arruda-Silva F, Gardiman E, Gasperini S, Calzetti F, Cassatella MA (2018) Cytokine production by human neutrophils: revisiting the “dark side of the moon”. Eur J Clin Invest:e12952. https://doi.org/10.1111/eci.12952 CrossRefPubMed

52.

Schön MP, Broekaert SM, Erpenbeck L (2017) Sexy again: the renaissance of neutrophils in psoriasis. Exp Dermatol 26:305–311. https://doi.org/10.1111/exd.13067 CrossRefPubMed

53.

Taylor PR, Roy S, Leal SM Jr, Sun Y, Howell SJ, Cobb BA, Li X, Pearlman E (2014) Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2. Nat Immunol 15:143–151. https://doi.org/10.1038/ni.2797 CrossRefPubMed

54.

Dyring-Andersen B, Honoré TV, Madelung A, Bzorek M, Simonsen S, Clemmensen SN, Clark RA, Borregaard N, Skov L (2017) Interleukin (IL)-17A and IL-22-producing neutrophils in psoriatic skin. Br J Dermatol 177:e321–e322. https://doi.org/10.1111/bjd.15533 CrossRefPubMedPubMedCentral

55.

Dudeck A, Suender CA, Kostka SL, von Stebut E, Maurer M (2011) Mast cells promote Th1 and Th17 responses by modulating dendritic cell maturation and function. Eur J Immunol 41:1883–1893. https://doi.org/10.1002/eji.201040994 CrossRefPubMed

56.

Noordenbos T, Blijdorp I, Chen S, Stap J, Mul E, Cañete JD, Lubberts E, Yeremenko N, Baeten D (2016) Human mast cells capture, store, and release bioactive, exogenous IL-17A. J Leukoc Biol 100:453–462. https://doi.org/10.1189/jlb.3HI1215-542R CrossRefPubMed

57.

Lories RJ, de Vlam K (2012) Is psoriatic arthritis a result of abnormalities in acquired or innate immunity? Curr Rheumatol Rep 14:375–382. https://doi.org/10.1007/s11926-012-0257-3 CrossRefPubMed

58.

Boutet MA, Nerviani A, Gallo Afflitto G, Pitzalis C (2018) Role of the IL-23/IL-17 axis in psoriasis and psoriatic arthritis: the clinical importance of its divergence in skin and joints. Int J Mol Sci 19. https://doi.org/10.3390/ijms19020530 CrossRefPubMedCentral

59.

Sakkas LI, Bogdanos DP (2017) Are psoriasis and psoriatic arthritis the same disease? The IL-23/IL-17 axis data. Autoimmun Rev 16:10–15. https://doi.org/10.1016/j.autrev.2016.09.015 CrossRefPubMed

60.

Suzuki E, Mellins ED, Gershwin ME, Nestle FO, Adamopoulos IE (2014) The IL-23/IL-17 axis in psoriatic arthritis. Autoimmun Rev 13:496–502. https://doi.org/10.1016/j.autrev.2014.01.050 CrossRefPubMedPubMedCentral

61.

Noordenbos T, Yeremenko N, Gofita I, van de Sande M, Tak PP, Caňete JD, Baeten D (2012) Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis. Arthritis Rheum 64:99–109. https://doi.org/10.1002/art.33396 CrossRefPubMed

62.

de Boer OJ, van der Meer JJ, Teeling P, van der Loos CM, Idu MM, van Maldegem F, Aten J, van der Wal AC (2010) Differential expression of interleukin-17 family cytokines in intact and complicated human atherosclerotic plaques. J Pathol 220:499–508. https://doi.org/10.1002/path.2667 CrossRefPubMed

63.

Guggino G, Ciccia F, Di Liberto D, Lo Pizzo M, Ruscitti P, Cipriani P, Ferrante A, Sireci G, Dieli F, Fournie JJ, Giacomelli R, Triolo G (2016) Interleukin (IL)-9/IL-9R axis drives γδ T cells activation in psoriatic arthritis patients. Clin Exp Immunol 186:277–283. https://doi.org/10.1111/cei.12853 CrossRefPubMedPubMedCentral

64.

Cai Y, Shen X, Ding C, Qi C, Li K, Li X, Jala VR, Zhang HG, Wang T, Zheng J, Yan J (2011) Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation. Immunity 35:596–610CrossRefPubMedPubMedCentral

65.

O'Brien RL, Born WK (2015) Dermal γδ T cells—what have we learned? Cell Immunol 296:62–69. https://doi.org/10.1016/j.cellimm.2015.01.011 CrossRefPubMedPubMedCentral

66.

van Baarsen LG, Lebre MC, van der Coelen D, Aarrass S, Tang MW, Ramwadhdoebe TH, Gerlag DM, Tak PP (2014) Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis, psoriatic arthritis and osteoarthritis: possible explanation for nonresponse to anti-IL-17 therapy? Arthritis Res Ther 16:426. https://doi.org/10.1186/s13075-014-0426-z CrossRefPubMedPubMedCentral

67.

Hartwig T, Pantelyushin S, Croxford AL, Kulig P, Becher B (2015) Dermal IL-17-producing γδ T cells establish long-lived memory in the skin. Eur J Immunol 45:3022–3033. https://doi.org/10.1002/eji.201545883 CrossRefPubMed

68.

Mabuchi T, Takekoshi T, Hwang ST (2011) Epidermal CCR6⁺ γδ T cells are major producers of IL-22 and IL-17 in a murine model of psoriasiform dermatitis. J Immunol 187:5026–5031. https://doi.org/10.4049/jimmunol.1101817 CrossRefPubMed

69.

Res PC, Piskin G, de Boer OJ, van der Loos CM, Teeling P, Bos JD, Teunissen MB (2010) Overrepresentation of IL-17A and IL-22 producing CD8 T cells in lesional skin suggests their involvement in the pathogenesis of psoriasis. PLoS One 5:e14108. https://doi.org/10.1371/journal.pone.0014108 CrossRefPubMedPubMedCentral

70.

Ortega C, Fernández-A S, Carrillo JM, Romero P, Molina IJ, Moreno JC, Santamaria M (2009) IL-17-producing CD8⁺ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines. J Leukoc Biol 86:435–443. https://doi.org/10.1189/JLB.0109046 CrossRefPubMed

71.

Hijnen D, Knol EF, Gent YY, Giovannone B, Beijn SJ, Kupper TS, Bruijnzeel-Koomen CA, Clark RA (2013) CD8⁺ T cells in the lesional skin of atopic dermatitis and psoriasis patients are an important source of IFN-ɣ, IL-13, IL-17, and IL-22. J Invest Dermatol 133:973–979. https://doi.org/10.1038/jid.2012.456 CrossRefPubMed

72.

Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS, Bowman EP, Krueger JG (2008) Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 128:1207–1211. https://doi.org/10.1038/sj.jid.5701213 CrossRefPubMed

73.

Harper EG, Guo C, Rizzo H, Lillis JV, Kurtz SE, Skorcheva I, Purdy D, Fitch E, Iordanov M, Blauvelt A (2009) Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest Dermatol 129:2175–2183. https://doi.org/10.1038/jid.2009.65 CrossRefPubMedPubMedCentral

74.

Mabuchi T, Singh TP, Takekoshi T, Jia GF, Wu X, Kao MC, Weiss I, Farber JM, Hwang ST (2013) CCR6 is required for epidermal trafficking of γδ-T cells in an IL-23-induced model of psoriasiform dermatitis. J Invest Dermatol 133:164–171. https://doi.org/10.1038/jid.2012.260 CrossRefPubMed

75.

Kim TG, Jee H, Fuentes-Duculan J, Wu WH, Byamba D, Kim DS, Kim DY, Lew DH, Yang WI, Krueger JG, Lee MG (2014) Dermal clusters of mature dendritic cells and T cells are associated with the CCL20/CCR6 chemokine system in chronic psoriasis. J Invest Dermatol 134:1462–1465. https://doi.org/10.1038/jid.2013.534 CrossRefPubMed

76.

Hedrick MN, Lonsdorf AS, Hwang ST, Farber JM (2010) CCR6 as a possible therapeutic target in psoriasis. Expert Opin Ther Targets 14:911–922. https://doi.org/10.1517/14728222.2010.504716 CrossRefPubMedPubMedCentral

77.

Hedrick MN, Lonsdorf AS, Shirakawa AK, Richard Lee CC, Liao F, Singh SP, Zhang HH, Grinberg A, Love PE, Hwang ST, Farber JM (2009) CCR6 is required for IL-23-induced psoriasis-like inflammation in mice. J Clin Invest 119:2317–2329CrossRefPubMedPubMedCentral

78.

Ward NL, Umetsu DT (2014) A new player on the psoriasis block: IL-17A- and IL-22-producing innate lymphoid cells. J Invest Dermatol 134:2305–2307. https://doi.org/10.1038/jid.2014.216 CrossRefPubMedPubMedCentral

79.

Teunissen MBM, Munneke JM, Bernink JH, Spuls PI, Res PCM, Te Velde A, Cheuk S, Brouwer MWD, Menting SP, Eidsmo L, Spits H, Hazenberg MD, Mjösberg J (2014) Composition of innate lymphoid cell subsets in the human skin: enrichment of NCR⁺ ILC3 in lesional skin and blood of psoriasis patients. J Invest Dermatol 134:2351–2360. https://doi.org/10.1038/jid.2014.146 CrossRefPubMed

80.

Tait Wojno ED, Artis D (2012) Innate lymphoid cells: balancing immunity, inflammation, and tissue repair in the intestine. Cell Host Microbe 12:445–457. https://doi.org/10.1016/j.chom.2012.10.003 CrossRefPubMed

81.

Johnston A, Guzman AM, Swindell WR, Wang F, Kang S, Gudjonsson JE (2014) Early tissue responses in psoriasis to the antitumour necrosis factor-α biologic etanercept suggest reduced interleukin-17 receptor expression and signalling. Br J Dermatol 171:97–107. https://doi.org/10.1111/bjd.12937 CrossRefPubMedPubMedCentral

82.

Rizzo HL, Kagami S, Phillips KG, Kurtz SE, Jacques SL, Blauvelt A (2011) IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A. J Immunol 186:1495–1502. https://doi.org/10.4049/jimmunol.1001001 CrossRefPubMed

83.

Puig L (2017) The role of IL 23 in the treatment of psoriasis. Expert Rev Clin Immunol 13:525–534. https://doi.org/10.1080/1744666X.2017.1292137 CrossRefPubMed

84.

Fitch E, Harper E, Skorcheva I, Kurtz SE, Blauvelt A (2007) Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Curr Rheumatol Rep 9:461–467CrossRefPubMedPubMedCentral

85.

St Leger AJ, Hansen AM, Karauzum H, Horai R, Yu CR, Laurence A, Mayer-Barber KD, Silver P, Villasmil R, Egwuagu C, Datta SK, Caspi RR (2018) STAT-3-independent production of IL-17 by mouse innate-like alphaβ T cells controls ocular infection. J Exp Med 215:1079–1090. https://doi.org/10.1084/jem.20170369 CrossRefPubMedPubMedCentral

86.

Yoshiga Y, Goto D, Segawa S, Ohnishi Y, Matsumoto I, Ito S, Tsutsumi A, Taniguchi M, Sumida T (2008) Invariant NKT cells produce IL-17 through IL-23-dependent and -independent pathways with potential modulation of Th17 response in collagen-induced arthritis. Int J Mol Med 22:369–374PubMed

87.

Miossec P, Kolls JK (2012) Targeting IL-17 and T_H17 cells in chronic inflammation. Nat Rev Drug Discov 11:763–776. https://doi.org/10.1038/nrd3794 CrossRefPubMed

88.

Zenobia C, Hajishengallis G (2015) Basic biology and role of interleukin-17 in immunity and inflammation. Periodontol 69:142–159. https://doi.org/10.1111/prd.12083 CrossRef

89.

Chiricozzi A, Krueger JG (2013) IL-17 targeted therapies for psoriasis. Expert Opin Investig Drugs 22:993–1005. https://doi.org/10.1517/13543784.2013.806483 CrossRefPubMed

90.

Erbel C, Akhavanpoor M, Okuyucu D, Wangler S, Dietz A, Zhao L, Stellos K, Little KM, Lasitschka F, Doesch A, Hakimi M, Dengler TJ, Giese T, Blessing E, Katus HA, Gleissner CA (2014) IL-17A influences essential functions of the monocyte/macrophage lineage and is involved in advanced murine and human atherosclerosis. J Immunol 193:4344–4355. https://doi.org/10.4049/jimmunol.1400181 CrossRefPubMedPubMedCentral

91.

Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, Gordon KB, Phoenix Study Investigators (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 371:1665–1674. https://doi.org/10.1016/S0140-6736(08)60725-4 CrossRefPubMed

92.

Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, Li S, Kimball AB (2017) Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol 76:405–417. https://doi.org/10.1016/j.jaad.2016.11.041 CrossRefPubMed

93.

Reich K, Papp KA, Blauvelt A, Tyring SK, Sinclair R, Thaçi D, Nograles K, Mehta A, Cichanowitz N, Li Q, Liu K, La Rosa C, Green S, Kimball AB (2017) Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet 390:276–288. https://doi.org/10.1016/S0140-6736(17)31279-5 CrossRefPubMed

94.

Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG, Lacour JP, Menter A, Philipp S, Sofen H, Tyring S, Berner BR, Visvanathan S, Pamulapati C, Bennett N, Flack M, Scholl P, Padula SJ (2017) Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med 376:1551–1560. https://doi.org/10.1056/NEJMoa1607017 CrossRefPubMed

95.

Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, Cameron GS, Erickson J, Zhang L, Secrest RJ, Ball S, Braun DK, Osuntokun OO, Heffernan MP, Nickoloff BJ, Papp K, UNCOVER-2 and UNCOVER-3 Investigators (2015) Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet 386:541–551. https://doi.org/10.1016/S0140-6736(15)60125-8 CrossRefPubMed

96.

Papp KA, Merola JF, Gottlieb AB, Griffiths CEM, Cross N, Peterson L, Cioffi C, Blauvelt A (2018) Dual neutralization of both interleukin 17A and interleukin 17F with bimekizumab in patients with psoriasis: results from BE ABLE 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial. J Am Acad Dermatol 79:277–286. https://doi.org/10.1016/j.jaad.2018.03.037 CrossRefPubMed

97.

Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, Papp K, Spelman L, Toth D, Kerdel F, Armstrong AW, Stingl G, Kimball AB, Bachelez H, Wu JJ, Crowley J, Langley RG, Blicharski T, Paul C, Lacour JP, Tyring S, Kircik L, Chimenti S, Callis Duffin K, Bagel J, Koo J, Aras G, Li J, Song W, Milmont CE, Shi Y, Erondu N, Klekotka P, Kotzin B, Nirula A (2015) Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med 373:1318–1328. https://doi.org/10.1056/NEJMoa1503824 CrossRefPubMed

98.

Gaspari AA, Tyring S (2015) New and emerging biologic therapies for moderate-to-severe plaque psoriasis: mechanistic rationales and recent clinical data for IL-17 and IL-23 inhibitors. Dermatol Ther 28:179–193. https://doi.org/10.1111/dth.12251 CrossRefPubMedPubMedCentral

99.

Blauvelt A, Lebwohl MG, Bissonnette R (2015) IL-23/IL-17A dysfunction phenotypes inform possible clinical effects from anti-IL-17A therapies. J Invest Dermatol 135:1946–1953. https://doi.org/10.1038/jid.2015.144 CrossRefPubMedPubMedCentral

100.

Girolomoni G, Strohal R, Puig L, Bachelez H, Barker J, Boehncke WH, Prinz JC (2017) The role of IL-23 and the IL-23/TH 17 immune axis in the pathogenesis and treatment of psoriasis. J Eur Acad Dermatol Venereol 31:1616–1626. https://doi.org/10.1111/jdv.14433 CrossRefPubMedPubMedCentral

101.

Nakamura M, Lee K, Jeon C, Sekhon S, Afifi L, Yan D, Lee K, Bhutani T (2017) Guselkumab for the treatment of psoriasis: a review of phase III trials. Dermatol Ther (Heidelb) 7:281–292. https://doi.org/10.1007/s13555-017-0187-0 CrossRef

102.

O'Connor W Jr, Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y, Kolls JK, Flavell RA (2009) A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol 10:603–609. https://doi.org/10.1038/ni.1736 CrossRefPubMedPubMedCentral

103.

Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, Wehkamp J, Feagan BG, Yao MD, Karczewski M, Karczewski J, Pezous N, Bek S, Bruin G, Mellgard B, Berger C, Londei M, Bertolino AP, Tougas G, Travis SP, Secukinumab in Crohn’s Disease Study Group (2012) Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 61:1693–1700. https://doi.org/10.1136/gutjnl-2011-301668 CrossRefPubMed

104.

Xu XR, Liu CQ, Feng BS, Liu ZJ (2014) Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease. World J Gastroenterol 20:3255–3264. https://doi.org/10.3748/wjg.v20.i12.3255 CrossRefPubMedPubMedCentral

105.

Targan SR, Feagan B, Vermeire S, Panaccione R, Melmed GY, Landers C, Li D, Russell C, Newmark R, Zhang N, Chon Y, Hsu YH, Lin SL, Klekotka P (2016) A randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn's disease. Am J Gastroenterol 111:1599–1607. https://doi.org/10.1038/ajg.2016.298 CrossRefPubMed

106.

Lee JS, Tato CM, Joyce-Shaikh B, Gulen MF, Cayatte C, Chen Y, Blumenschein WM, Judo M, Ayanoglu G, McClanahan TK, Li X, Cua DJ (2015) Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity 43:727–738. https://doi.org/10.1016/j.immuni.2015.09.003 CrossRefPubMedPubMedCentral

107.

Marwaha AK, Leung NJ, McMurchy AN, Levings MK (2012) TH17 cells in autoimmunity and immunodeficiency: protective or pathogenic? Front Immunol 3:129. https://doi.org/10.3389/fimmu.2012.00129 CrossRefPubMedPubMedCentral

108.

Li L, Boussiotis VA (2013) The role of IL-17-producing Foxp3+ CD4+ T cells in inflammatory bowel disease and colon cancer. Clin Immunol 148:246–253. https://doi.org/10.1016/j.clim.2013.05.003 CrossRefPubMed

109.

Blauvelt A (2016) Safety of secukinumab in the treatment of psoriasis. Expert Opin Drug Saf 15:1413–1420. https://doi.org/10.1080/14740338.2016.1221923 CrossRefPubMed

110.

van de Kerkhof PC, Griffiths CE, Reich K, Leonardi CL, Blauvelt A, Tsai TF, Gong Y, Huang J, Papavassilis C, Fox T (2016) Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol 75:83–98.e4. https://doi.org/10.1016/j.jaad.2016.03.024 CrossRefPubMed

111.

Reich K, Leonardi C, Langley RG, Warren RB, Bachelez H, Romiti R, Ohtsuki M, Xu W, Acharya N, Solotkin K, Colombel JF, Hardin DS (2017) Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: a presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials. J Am Acad Dermatol 76:441–448.e2. https://doi.org/10.1016/j.jaad.2016.10.027 CrossRefPubMed

112.

Hohenberger M, Cardwell LA, Oussedik E, Feldman SR (2018) Interleukin-17 inhibition: role in psoriasis and inflammatory bowel disease. J Dermatolog Treat 29:13–18. https://doi.org/10.1080/09546634.2017.1329511 CrossRefPubMed

113.

Armstrong AW, Bukhalo M, Blauvelt A (2016) A clinician's guide to the diagnosis and treatment of candidiasis in patients with psoriasis. Am J Clin Dermatol 17:329–336. https://doi.org/10.1007/s40257-016-0206-4 CrossRefPubMedPubMedCentral

114.

Lebwohl MG, Papp KA, Marangell LB, Koo J, Blauvelt A, Gooderham M, Wu JJ, Rastogi S, Harris S, Pillai R, Israel RJ (2018) Psychiatric adverse events during treatment with brodalumab: analysis of psoriasis clinical trials. J Am Acad Dermatol 78:81–89 e85. https://doi.org/10.1016/j.jaad.2017.08.024 CrossRefPubMed

115.

Rieder EA (2018) In response to Lebwohl et al, “psychiatric adverse events during treatment with brodalumab: analysis of psoriasis clinical trials”. J Am Acad Dermatol 78:e73. https://doi.org/10.1016/j.jaad.2017.10.052 CrossRefPubMed

116.

Chiricozzi A, Romanelli M, Saraceno R, Torres T (2016) No meaningful association between suicidal behavior and the use of IL-17A-neutralizing or IL-17RA-blocking agents. Expert Opin Drug Saf 15:1653–1659. https://doi.org/10.1080/14740338.2016.1228872 CrossRefPubMed

117.

Clark RA (2011) Gone but not forgotten: lesional memory in psoriatic skin. J Invest Dermatol 131:283–285. https://doi.org/10.1038/jid.2010.374 CrossRefPubMedPubMedCentral

118.

Suárez-Fariñas M, Fuentes-Duculan J, Lowes MA, Krueger JG (2011) Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol 131:391–400. https://doi.org/10.1038/jid.2010.280 CrossRefPubMed

119.

Johnson-Huang LM, Pensabene CA, Shah KR, Pierson KC, Kikuchi T, Lentini T, Gilleaudeau P, Sullivan-Whalen M, Cueto I, Khatcherian A, Hyder LA, Suárez-Fariñas M, Krueger JG, Lowes MA (2012) Post-therapeutic relapse of psoriasis after CD11a blockade is associated with T cells and inflammatory myeloid DCs. PLoS One 7:e30308. https://doi.org/10.1371/journal.pone.0030308 CrossRefPubMedPubMedCentral

120.

Matos TR, O'Malley JT, Lowry EL, Hamm D, Kirsch IR, Robins HS, Kupper TS, Krueger JG, Clark RA (2017) Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing αβ T cell clones. J Clin Invest 127:4031–4041. https://doi.org/10.1172/JCI93396 CrossRefPubMedPubMedCentral

121.

Blauvelt A, Reich K, Tsai TF, Tyring S, Vanaclocha F, Kingo K, Ziv M, Pinter A, Vender R, Hugot S, You R, Milutinovic M, Thaçi D (2017) Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: results from the CLEAR study. J Am Acad Dermatol 76:60–69.e9. https://doi.org/10.1016/j.jaad.2016.08.008 CrossRefPubMed

122.

Kolbinger F, Loesche C, Valentin MA, Jiang X, Cheng Y, Jarvis P, Peters T, Calonder C, Bruin G, Polus F, Aigner B, Lee DM, Bodenlenz M, Sinner F, Pieber TR, Patel DD (2017) β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis. J Allergy Clin Immunol 139:923–932.e8. https://doi.org/10.1016/j.jaci.2016.06.038 CrossRefPubMed

123.

Loesche C, Kolbinger F, Valentin MA, Jarvis P, Ceci M, Wieczorek G, Khokhlovich E, Koroleva I, Bruin G, Sinner F, Aigner B, Patel DD (2016) Interleukin-17A blockade with secukinumab results in decreased neutrophil infiltration in psoriasis: minimally-invasive measurement by tape stripping. Adv Precision Med 1:1–9CrossRef

124.

Nirula A, Nilsen J, Klekotka P, Kricorian G, Erondu N, Towne JE, Russell CB, Martin DA, Budelsky AL (2016) Effect of IL-17 receptor a blockade with brodalumab in inflammatory diseases. Rheumatology (Oxford) 55:ii43–ii55. https://doi.org/10.1093/rheumatology/kew346 CrossRef

125.

Russell CB, Rand H, Bigler J, Kerkof K, Timour M, Bautista E, Krueger JG, Salinger DH, Welcher AA, Martin DA (2014) Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody. J Immunol 192:3828–3836. https://doi.org/10.4049/jimmunol.1301737 CrossRefPubMed

126.

Maroof A, Okoye R, Smallie T, Baeten D, Archer S, Simpson C, Griffiths M, Shaw S (2017) Bimekizumab dual inhibition of IL-17A and IL-17F provides evidence of IL-17F contribution to chronic inflammation in disease-relevant cells [abstract]. Arthritis Rheumatol 69(Suppl 10):Abstract 1571

127.

Maroof A, Baeten D, Archer S, Griffiths M, Shaw S (2017) IL-17F contributes to human chronic inflammation in synovial tissue: preclinical evidence with dual IL-17a and IL-17F inhibition with bimekizumab in psoriatic arthritis. Ann Rheum Dis 76:A13CrossRef

128.

Maroof A, Smallie T, Archer S, Simpson C, Griffiths M, Baeten D, Shaw S (2017) Dual IL-17A and IL-17F inhibition with bimekizumab provides evidence for IL-17F contribution in immune-mediated inflammatory skin response [abstract]. J Invest Dermatol 137:S120 Abstract 699CrossRef

129.

de Vlam K, Gottlieb AB, Mease PJ (2014) Current concepts in psoriatic arthritis: pathogenesis and management. Acta Derm Venereol 94:627–634. https://doi.org/10.2340/00015555-1833 CrossRefPubMed

130.

O'Rielly DD, Rahman P (2015) Genetic, epigenetic and pharmacogenetic aspects of psoriasis and psoriatic arthritis. Rheum Dis Clin N Am 41:623–642. https://doi.org/10.1016/j.rdc.2015.07.002 CrossRef

131.

Wang EA, Suzuki E, Maverakis E, Adamopoulos IE (2017) Targeting IL-17 in psoriatic arthritis. Eur J Rheumatol 4:272–277. https://doi.org/10.5152/eurjrheum.2017.17037 CrossRefPubMedPubMedCentral

132.

Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, Landewé R, Nash P, Pricop L, Yuan J, Richards HB, Mpofu S, FUTURE 1 Study Group (2015) Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med 373:1329–1339. https://doi.org/10.1056/NEJMoa1412679 CrossRefPubMed

133.

McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewé R, Conaghan PG, Gottlieb AB, Richards H, Pricop L, Ligozio G, Patekar M, Mpofu S, FUTURE 2 Study Group (2015) Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 386:1137–1146. https://doi.org/10.1016/S0140-6736(15)61134-5 CrossRefPubMed

134.

Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, Shuler CL, Lin CY, Braun DK, Lee CH, Gladman DD, SPIRIT-P1 Study Group (2017) Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis 76:79–87. https://doi.org/10.1136/annrheumdis-2016-209709 CrossRefPubMed

135.

Nash P, Kirkham B, Okada M, Rahman P, Combe B, Burmester GR, Adams DH, Kerr L, Lee C, Shuler CL, Genovese M, SPIRIT-P2 Study Group (2017) Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet 389:2317–2327. https://doi.org/10.1016/S0140-6736(17)31429-0 CrossRefPubMed

136.

Mease PJ, Genovese MC, Greenwald MW, Ritchlin CT, Beaulieu AD, Deodhar A, Newmark R, Feng J, Erondu N, Nirula A (2014) Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med 370:2295–2306. https://doi.org/10.1056/NEJMoa1315231 CrossRefPubMed

137.

Mitra A, Raychaudhuri SK, Raychaudhuri SP (2014) IL-17 and IL-17R: an auspicious therapeutic target for psoriatic disease. Actas Dermosifiliogr 105(Suppl 1):21–33. https://doi.org/10.1016/S0001-7310(14)70015-8 CrossRefPubMed

138.

Hashmi S, Zeng QT (2006) Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease. Coron Artery Dis 17:699–706. https://doi.org/10.1097/01.mca.0000236288.94553.b4 CrossRefPubMed

139.

Karbach S, Croxford AL, Oelze M, Schuler R, Minwegen D, Wegner J, Koukes L, Yogev N, Nikolaev A, Reißig S, Ullmann A, Knorr M, Waldner M, Neurath MF, Li H, Wu Z, Brochhausen C, Scheller J, Rose-John S, Piotrowski C, Bechmann I, Radsak M, Wild P, Daiber A, von Stebut E, Wenzel P, Waisman A, Münzel T (2014) Interleukin 17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease. Arterioscler Thromb Vasc Biol 34:2658–2668. https://doi.org/10.1161/ATVBAHA.114.304108 CrossRefPubMed

140.

Li Y, Golden JB, Camhi MI, Zhang X, Fritz Y, Diaconu D, Ivanco TL, Simon DI, Kikly K, McCormick TS, Wang Y, Ward NL (2018) Protection from psoriasis-related thrombosis after inhibition of IL-23 or IL-17A. J Invest Dermatol 138:310–315. https://doi.org/10.1016/j.jid.2017.09.021 CrossRefPubMed

141.

Simon T, Taleb S, Danchin N, Laurans L, Rousseau B, Cattan S, Montely JM, Dubourg O, Tedgui A, Kotti S, Mallat Z (2013) Circulating levels of interleukin-17 and cardiovascular outcomes in patients with acute myocardial infarction. Eur Heart J 34:570–577. https://doi.org/10.1093/eurheartj/ehs263 CrossRefPubMed

Title: The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis
Authors: Andrew Blauvelt
Andrea Chiricozzi
Publication date: 01-12-2018
Publisher: Springer US
Published in: Clinical Reviews in Allergy & Immunology / Issue 3/2018
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI: https://doi.org/10.1007/s12016-018-8702-3

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2018

Autoimmunity in 2017

Clinical Features of Psoriatic Arthritis: a Comprehensive Review of Unmet Clinical Needs

Unmet Needs in the Pathogenesis and Treatment of Cardiovascular Comorbidities in Chronic Inflammatory Diseases

Unmet Needs in the Field of Psoriasis: Pathogenesis and Treatment

Unmet Needs in Axial Spondyloarthritis

Unmet Needs in IBD: the Case of Fatigue

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage