Chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, spondyloarthritis, and psoriasis cause significant morbidity and are a considerable burden for the patients in terms of pain, impaired function, and diminished quality of life, as well as for society, because of the associated high health-care costs and loss of productivity. Our limited understanding of the pathogenic mechanisms involved in these diseases currently hinders early diagnosis and the development of more specific and effective therapies. The past years have been marked by considerable progress in our insight of the genetic basis of many diseases. In particular, genome-wide association studies (GWAS) performed with thousands of patients have provided detailed information about the genetic variants associated with a large number of chronic inflammatory diseases. These studies have brought to the forefront many genes linked to signaling pathways that were not previously known to be involved in pathogenesis, pointing to new directions in the study of disease mechanisms. GWAS also provided fundamental evidence for a key role of the immune system in the pathogenesis of these diseases, because many of the identified loci map to genes involved in different immune processes. However, the mechanisms by which disease-associated genetic variants act on disease development and the targeted cell populations remain poorly understood. The challenge of the post-GWAS era is to understand how these variants affect pathogenesis, to allow translation of genetic data into better diagnostics and innovative treatment strategies. Here, we review recent results that document the importance of the IL-23/IL-17 pathway for the pathogenesis of several chronic inflammatory diseases and summarize data that demonstrate how therapeutic targeting of this pathway can benefit affected patients.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
El-Gabalawy H, Guenther LC, Bernstein CN. Epidemiology of immune-mediated inflammatory diseases: incidence, prevalence, natural history, and comorbidities. J Rheumatol Suppl. 2010;85:2–10.
Parkes M, Cortes A, van Heel DA, Brown MA. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet. 2013;14:661–73.
Westra HJ, Martinez-Bonet M, Onengut-Gumuscu S, Lee A, Luo Y, Teslovich N, et al. Fine-mapping and functional studies highlight potential causal variants for rheumatoid arthritis and type 1 diabetes. Nat Genet. 2018;50:1366–74.
Diogo D, Bastarache L, Liao KP, Graham RR, Fulton RS, Greenberg JD, et al. TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits. PLoS ONE. 2015;10:e0122271.
Onengut-Gumuscu S, Chen WM, Burren O, Cooper NJ, Quinlan AR, Mychaleckyj JC, et al. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Nat Genet. 2015;47:381–6.
International Multiple Sclerosis Genetics Consortium, Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, Kemppinen A, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45:1353–60.
Hinks A, Cobb J, Marion MC, Prahalad S, Sudman M, Bowes J, et al. Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis. Nat Genet. 2013;45:664–9.
Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE, Capon F, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet. 2012;44:1341–8.
Ellinghaus D, Jostins L, Spain SL, Cortes A, Bethune J, Han B, et al. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nat Genet. 2016;48:510–8.
International Genetics of Ankylosing Spondylitis Consortium, Cortes A, Hadler J, Pointon JP, Robinson PC, Karaderi T, et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet. 2013;45:730–8.
Liu JZ, Almarri MA, Gaffney DJ, Mells GF, Jostins L, Cordell HJ, et al. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. Nat Genet. 2012;44:1137–41.
Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491:119–24.
Cotsapas C, Voight BF, Rossin E, Lage K, Neale BM, Wallace C, et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet. 2011;7:e1002254.
Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature. 2015;518:337–43.
Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.
Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet. 2008;40:955–62.
Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet. 2007;39:1329–37.
Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet. 2007;80:273–90.
Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, et al. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet. 2008;4:e1000041.
Letimier FA, Passini N, Gasparian S, Bianchi E, Rogge L. Chromatin remodeling by the SWI/SNF-like BAF complex and STAT4 activation synergistically induce IL-12Rbeta2 expression during human Th1 cell differentiation. EMBO J. 2007;26:1292–302.
Roberts AR, Vecellio M, Chen L, Ridley A, Cortes A, Knight JC, et al. An ankylosing spondylitis-associated genetic variant in the IL23R-IL12RB2 intergenic region modulates enhancer activity and is associated with increased Th1-cell differentiation. Ann Rheum Dis. 2016;75:2150–6.
Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007;8:639–46.
Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, et al. Phenotypic and functional features of human Th17 cells. J Exp Med. 2007;204:1849–61.
Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715–25.
Steinman L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med. 2007;13:139–45.
Trinchieri G, Pflanz S, Kastelein RA. The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity. 2003;19:641–4.
Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002;168:5699–708.
Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney 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.
Bettelli E, Kuchroo VK. IL-12- and IL-23-induced T helper cell subsets: birds of the same feather flock together. J Exp Med. 2005;201:169–71.
Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201:233–40.
Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744–8.
Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003;198:1951–7.
Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med. 2006;203:2473–83.
Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, 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.
Chen Y, Langrish CL, McKenzie B, Joyce-Shaikh B, Stumhofer JS, McClanahan T, et al. Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest. 2006;116:1317–26.
Kroenke MA, Carlson TJ, Andjelkovic AV, Segal BM. IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J Exp Med. 2008;205:1535–41.
Stromnes IM, Cerretti LM, Liggitt D, Harris RA, Goverman JM. Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells. Nat Med. 2008;14:337–42.
McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 2009;10:314–24.
Buonocore S, Ahern PP, Uhlig HH, Ivanov II, Littman DR, Maloy KJ, et al. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature. 2010;464:1371–5.
Geremia A, Arancibia-Carcamo CV, Fleming MP, Rust N, Singh B, Mortensen NJ, et al. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med. 2011;208:1127–33.
Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity. 2009;31:331–41.
Kenna TJ, Davidson SI, Duan R, Bradbury LA, McFarlane J, Smith M, et al. Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive gamma/delta T cells in patients with active ankylosing spondylitis. Arthritis Rheum. 2012;64:1420–9.
Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, et al. IL-23 induces spondyloarthropathy by acting on ROR-gammat(+) CD3(+)CD4(−)CD8(−) entheseal resident T cells. Nat Med. 2012;18:1069–76.
Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis—insights into pathogenesis. Nat Rev Rheumatol. 2016;12:81–91.
Coffre M, Roumier M, Rybczynska M, Sechet E, Law HK, Gossec L, et al. Combinatorial control of Th17 and Th1 cell functions by genetic variations in genes associated with the interleukin-23 signaling pathway in spondyloarthritis. Arthritis Rheum. 2013;65:1510–21.
Di Meglio P, Di Cesare A, Laggner U, Chu CC, Napolitano L, Villanova F, et al. The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans. PLoS ONE. 2011;6:e17160.
Sarin R, Wu X, Abraham C. Inflammatory disease protective R381Q IL23 receptor polymorphism results in decreased primary CD4+ and CD8+ human T-cell functional responses. Proc Natl Acad Sci USA. 2011;108:9560–5.
Fairfax BP, Humburg P, Makino S, Naranbhai V, Wong D, Lau E, et al. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science. 2014;343:1246949.
Knight JC. Approaches for establishing the function of regulatory genetic variants involved in disease. Genome Med. 2014;6:92.
Piasecka B, Duffy D, Urrutia A, Quach H, Patin E, Posseme C, et al. Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges. Proc Natl Acad Sci USA. 2018;115:E488–97.
Dendrou CA, Cortes A, Shipman L, Evans HG, Attfield KE, Jostins L, et al. Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Sci Transl Med. 2016;8:363ra149.
Velazquez L, Fellous M, Stark GR, Pellegrini S. A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell. 1992;70:313–22.
Minegishi Y, Saito M, Morio T, Watanabe K, Agematsu K, Tsuchiya S, et al. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity. 2006;25:745–55.
Kreins AY, Ciancanelli MJ, Okada S, Kong XF, Ramirez-Alejo N, Kilic SS, et al. Human TYK2 deficiency: mycobacterial and viral infections without hyper-IgE syndrome. J Exp Med. 2015;212:1641–62.
Boisson-Dupuis S, Ramirez-Alejo N, Li Z, Patin E, Rao G, Kerner G, et al. Tuberculosis and impaired IL-23-dependent IFN-gamma immunity in humans homozygous for a common TYK2 missense variant. Sci Immunol. 2018;3:eaau8714.
Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, et al. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science. 1998;280:1432–5.
Boisson-Dupuis S, Bustamante J, El-Baghdadi J, Camcioglu Y, Parvaneh N, El Azbaoui S, et al. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood. Immunol Rev. 2015;264:103–20.
de Jong R, Altare F, Haagen IA, Elferink DG, Boer T, van Breda Vriesman PJ, et al. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science. 1998;280:1435–8.
Papp K, Gordon K, Thaci D, Morita A, Gooderham M, Foley P, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379:1313–21.
Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–33.
Withers DR, Hepworth MR, Wang X, Mackley EC, Halford EE, Dutton EE, et al. Transient inhibition of ROR-gammat therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells. Nat Med. 2016;22:319–23.
Bassolas-Molina H, Raymond E, Labadia M, Wahle J, Ferrer-Picon E, Panzenbeck M, et al. An RORgammat oral inhibitor modulates IL-17 responses in peripheral blood and intestinal mucosa of Crohn’s disease patients. Front Immunol. 2018;9:2307.
Venken K, Jacques P, Mortier C, Labadia ME, Decruy T, Coudenys J, et al. RORgammat inhibition selectively targets IL-17 producing iNKT and gammadelta-T cells enriched in Spondyloarthritis patients. Nat Commun. 2019;10:9.
Cyr P, Bronner SM, Crawford JJ. Recent progress on nuclear receptor RORgamma modulators. Bioorg Med Chem Lett. 2016;26:4387–93.
Pandya VB, Kumar S, Sachchidanand, Sharma R, Desai RC. Combating autoimmune diseases with retinoic acid receptor-related orphan receptor-gamma (RORgamma or RORc) inhibitors: hits and misses. J Med Chem. 2018. https://doi.org/10.1021/acs.jmedchem.8b00588. [Epub ahead of print].
Guo Y, MacIsaac KD, Chen Y, Miller RJ, Jain R, Joyce-Shaikh B, et al. Inhibition of RORgammaT skews TCRalpha gene rearrangement and limits T cell repertoire diversity. Cell Rep. 2016;17:3206–18.
Okada S, Markle JG, Deenick EK, Mele F, Averbuch D, Lagos M, et al. IMMUNODEFICIENCIES. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science. 2015;349:606–13.
Liljevald M, Rehnberg M, Soderberg M, Ramnegard M, Borjesson J, Luciani D, et al. Retinoid-related orphan receptor gamma (RORgamma) adult induced knockout mice develop lymphoblastic lymphoma. Autoimmun Rev. 2016;15:1062–70.
Krueger GG, Langley RG, Leonardi C, Yeilding N, Guzzo C, Wang Y, et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med. 2007;356:580–92.
Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, et al. 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. 2008;371:1665–74.
Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371:1675–84.
Griffiths CE, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362:118–28.
Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG, Lacour JP, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376:1551–60.
Li J, Vinh DC, Casanova JL, Puel A. Inborn errors of immunity underlying fungal diseases in otherwise healthy individuals. Curr Opin Microbiol. 2017;40:46–57.
Jeon C, Sekhon S, Yan D, Afifi L, Nakamura M, Bhutani T. Monoclonal antibodies inhibiting IL-12, -23, and -17 for the treatment of psoriasis. Hum Vaccines Immunother. 2017;13:2247–59.
Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, et al. 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. 2012;61:1693–700.
Targan SR, Feagan B, Vermeire S, Panaccione R, Melmed GY, Landers C, et al. A randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn’s disease. Am J Gastroenterol. 2016;111:1599–607.
Lee JS, Tato CM, Joyce-Shaikh B, Gulen MF, Cayatte C, Chen Y, et al. Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity. 2015;43:727–38.
Maxwell JR, Zhang Y, Brown WA, Smith CL, Byrne FR, Fiorino M, et al. Differential roles for interleukin-23 and interleukin-17 in intestinal immunoregulation. Immunity. 2015;43:739–50.
De Vos M, Mielants H, Cuvelier C, Elewaut A, Veys E. Long-term evolution of gut inflammation in patients with spondyloarthropathy. Gastroenterology. 1996;110:1696–703.
Van Praet L, Van den Bosch FE, Jacques P, Carron P, Jans L, Colman R, et al. Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model. Ann Rheum Dis. 2013;72:414–7.
Schreiber S, Colombel JF, Feagan BG, Reich K, Deodhar AA, McInnes IB, et al. Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials. Ann Rheum Dis. 2019;78:473–9.
Feagan BG, Sandborn WJ, D’Haens G, Panes J, Kaser A, Ferrante M, et al. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn’s disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017;389:1699–709.
Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375:1946–60.
Baeten D, Ostergaard M, Wei JC, Sieper J, Jarvinen P, Tam LS, et al. Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis. 2018;77:1295–302.
Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382:1705–13.
Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373:2534–48.
Jandus C, Bioley G, Rivals JP, Dudler J, Speiser D, Romero P. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008;58:2307–17.
Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 2009;60:1647–56.
Bowness P, Ridley A, Shaw J, Chan AT, Wong-Baeza I, Fleming M, et al. Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis. J Immunol. 2011;186:2672–80.
van der Heijde D, Ramiro S, Landewe R, Baraliakos X, Van den Bosch F, Sepriano A, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76:978–91.
Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371:326–38.
McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, et al. 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. 2015;386:1137–46.
Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373:1329–39.
van Mens LJJ, van de Sande MGH, Menegatti S, Chen S, Blijdorp ICJ, de Jong HM, et al. Brief report: interleukin-17 blockade with secukinumab in peripheral spondyloarthritis impacts synovial immunopathology without compromising systemic immune responses. Arthritis Rheumatol. 2018;70:1994–2002.
Blijdorp ICJ, Menegatti S, van Mens LJJ, van de Sande MGH, Chen S, Hreggvidsdottir HS, et al. Expansion of interleukin-22- and granulocyte-macrophage colony-stimulating factor-expressing, but not interleukin-17A-expressing, group 3 innate lymphoid cells in the inflamed joints of patients with spondyloarthritis. Arthritis Rheumatol. 2019;71:392–402.
Sinigaglia F, D’Ambrosio D, Panina-Bordignon P, Rogge L. Regulation of the IL-12/IL-12R axis: a critical step in T-helper cell differentiation and effector function. Immunol Rev. 1999;170:65–72.
The authors thank Sandra Pellegrini and Zhi Li for helpful discussions.
Work in the authors’ laboratory was supported by grants from Institut Pasteur, FOREUM Foundation for Research in Rheumatology, the Fondation Arthritis and MSD Avenir (Project iCARE-SpA).
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Bianchi, E., Rogge, L. The IL-23/IL-17 pathway in human chronic inflammatory diseases—new insight from genetics and targeted therapies. Genes Immun 20, 415–425 (2019). https://doi.org/10.1038/s41435-019-0067-y
This article is cited by
Research advances in the role and pharmaceuticals of ATP-binding cassette transporters in autoimmune diseases
Molecular and Cellular Biochemistry (2022)
Peripheral Enthesitis in Spondyloarthritis: Lessons from Targeted Treatments