Ustekinumab in psoriasis immunopathology with emphasis on the Th17-IL23 axis. A primer.

[en] Psoriasis is a chronic relapsing immunoinflammatory dermatosis that is commonly associated with systemic comorbidities. The pathogenic importance of interleukin (IL)-12 and IL-23 is beyond doubt, as well as the involvement of T helper cells (Th)1 and Th17 cells. There is upregulation of the p40 subunit shared by IL-12 and IL-23 and of the IL-23 p19 subunit, but not an increased expression of the IL-12 p35 subunit. This indicates that IL-23 appears more involved than IL-12 in the pathogenesis of psoriatic plaques. Ustekinumab is a fully human monoclonal antibody of the immunoglobulin (Ig) G1 class targeting the p40 subunit common to both IL-12 and IL-23, thus inhibiting both IL-12 and IL-23 receptor-mediated signalling. Ustekinumab is part of the recent biologic therapies active in psoriasis, autoimmune arthritides, and inflammatory bowel diseases.

Disciplines :

Dermatology

Author, co-author :

QUATRESOOZ, Pascale ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie

Hermanns-Lê, Trinh ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie

Pierard, Gérald ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques

Humbert, Philippe

DELVENNE, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique

FRANCHIMONT, Claudine ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie

Language :

English

Title :

Ustekinumab in psoriasis immunopathology with emphasis on the Th17-IL23 axis. A primer.

Publication date :

2012

Journal title :

Journal of Biomedicine and Biotechnology

ISSN :

1110-7243

eISSN :

1110-7251

Publisher :

Hindawi, United States

Volume :

2012

Issue :

147413

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 23 July 2012

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Bibliography

Piérard G. E., Piérard-Franchimont C., Szepetiuk G., Paquet P., Quatresooz P., The therapeutic potential of TNF- antagonists for skin psoriasis comorbidities Expert Opinion on Biological Therapy 2010 10 8 1197 1208
Nickoloff B. J., Nestle F. O., Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities Journal of Clinical Investigation 2004 113 12 1664 1675 (Pubitemid 39071656)
Griffiths C. E., Barker J. N., Pathogenesis and clinical features of psoriasis The Lancet 2007 370 9583 263 271 (Pubitemid 47069537)
Nestle F. O., Kaplan D. H., Barker J., Mechanisms of disease: psoriasis New England Journal of Medicine 2009 361 5 444 509
Kurzeja M., Rudnicka L., Olszewska M., New interleukin-23 pathway inhibitors in dermatology: ustekinumab, briakinumab, and secukinumab American Journal of Clinical Dermatology 2011 12 2 113 125
Yeilding N., Szapary P., Brodmerkel C., Benson J., Plotnick M., Zhou H., Goyal K., Schenkel B., Giles-Komar J., Mascelli M. A., Guzzo C., Development of the IL-12/23 antagonist ustekinumab in psoriasis: past, present, and future perspectives Annals of the New York Academy of Sciences 2011 1222 1 30 39
Nickoloff B. J., Nestle F. O., Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities Journal of Clinical Investigation 2004 113 12 1664 1675 (Pubitemid 39071656)
Menter A., Gottlieb A., Feldman S. R., Van Voorhees A. S., Leonardi C. L., Gordon K. B., Lebwohl M., Koo J. Y. M., Elmets C. A., Korman N. J., Beutner K. R., Bhushan R., Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics Journal of the American Academy of Dermatology 2008 58 5 826 850 (Pubitemid 351509656)
Lyakh L., Trinchieri G., Provezza L., Carra G., Gerosa F., Regulation of interleukin-12/interleukin-23 production and the T-helper 17 response in humans Immunological Reviews 2008 226 1 112 131
Trinchieri G., Interleukin-12 and the regulation of innate resistance and adaptive immunity Nature Reviews Immunology 2003 3 2 133 146 (Pubitemid 37328691)
Oppmann B., Lesley R., Blom B., Timans J. C., Xu Y., Hunte B., Vega F., Yu N., Wang J., Singh K., Zonin F., Vaisberg E., Churakova T., Liu M. R., Gorman D., Wagner J., Zurawski S., Liu Y. J., Abrams J. S., Moore K. W., Rennick D., De Waal-Malefyt R., Hannum C., Bazan J. F., Kastelein R. A., 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 5 715 725
Aggarwal S., Ghilardi N., Xie M. H., De Sauvage F. J., Gurney A. L., Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 Journal of Biological Chemistry 2003 278 3 1910 1914 (Pubitemid 36801431)
Wilson N. J., Boniface K., Chan J. R., McKenzie B. S., Blumenschein W. M., Mattson J. D., Basham B., Smith K., Chen T., Morel F., Lecron J. C., Kastelein R. A., Cua D. J., McClanahan T. K., Bowman E. P., Malefyt R. D. W., Development, cytokine profile and function of human interleukin 17-producing helper T cells Nature Immunology 2007 8 9 950 957 (Pubitemid 47300009)
Presky D. H., Yang H., Minetti L. J., Chua A. O., Nabavi N., Wu C. Y., Gately M. K., Gubler U., A functional interleukin 12 receptor complex is composed of two -type cytokine receptor subunits Proceedings of the National Academy of Sciences of the United States of America 1996 93 24 14002 14007
Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., Pflanz S., Zhang R., Singh K. P., Vega F., To W., Wagner J., O'Farrell A. M., McClanahan T., Zurawski S., Hannum C., Gorman D., Rennick D. M., Kastelein R. A., De Waal Malefyt R., Moore K. W., A receptor for the heterodimeric cytokine IL-23 is composed of IL-12R 1 and a novel cytokine receptor subunit, IL-23R Journal of Immunology 2002 168 11 5699 5708 (Pubitemid 34556153)
Yang L., Anderson D. E., Baecher-Allan C., Hastings W. D., Bettelli E., Oukka M., Kuchroo V. K., Hafler D. A., IL-21 and TGF- are required for differentiation of human T H17 cells Nature 2008 454 7202 350 352
Nestle F. O., Conrad C., The IL-12 family member p40 chain as a master switch and novel therapeutic target in psoriasis Journal of Investigative Dermatology 2004 123 6 14 15
Nickoloff B. J., Cracking the cytokine code in psoriasis Nature Medicine 2007 13 3 242 244 (Pubitemid 46376653)
Lowes M. A., Kikuchi T., Fuentes-Duculan J., Cardinale I., Zaba L. C., Haider A. S., Bowman E. P., Krueger J. G., Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells Journal of Investigative Dermatology 2008 128 5 1207 1211 (Pubitemid 351543220)
Piskin G., Sylva-Steenland R. M. R., Bos J. D., Teunissen M. B. M., In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin Journal of Immunology 2006 176 3 1908 1915 (Pubitemid 43134336)
Torti D. C., Feldman S. R., Interleukin-12, interleukin-23, and psoriasis: currentprospects Journal of the American Academy of Dermatology 2007 57 6 1059 1068
Kimball A. B., Gordon K. B., Langley R. G., Menter A., Chartash E. K., Valdes J., Safety and efficacy of ABT-874, a fully human interleukin 12/23 monoclonal antibody, in the treatment of moderate to severe chronic plaque psoriasis: results of a randomized, placebo-controlled, phase 2 trial Archives of Dermatology 2008 144 2 200 207 (Pubitemid 351287002)
Cargill M., Schrodi S. J., Chang M., Garcia V. E., Brandon R., Callis K. P., Matsunami N., Ardlie K. G., Civello D., Catanese J. J., Leong D. U., Panko J. M., McAllister L. B., Hansen C. B., Papenfuss J., Prescott S. M., White T. J., Leppert M. F., Krueger G. G., Begovich A. B., A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes American Journal of Human Genetics 2007 80 2 273 290 (Pubitemid 46175676)
Duerr R. H., Taylor K. D., Brant S. R., Rioux J. D., Silverberg M. S., Daly M. J., Steinhart A. H., Abraham C., Regueiro M., Griffiths A., Dassopoulos T., Bitton A., Yang H., Targan S., Datta L. W., Kistner E. O., Schumm L. P., Lee A. T., Gregersen P. K., Barmada M. M., Rotter J. I., Nicolae D. L., Cho J. H., A genome-wide association study identifies IL23R as an inflammatory bowel disease gene Science 2006 314 5804 1461 1463 (Pubitemid 44871953)
Capon F., Di Meglio P., Szaub J., Prescott N. J., Dunster C., Baumber L., Timms K., Gutin A., Abkevic V., Burden A. D., Lanchbury J., Barker J. N., Trembath R. C., Nestle F. O., Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis Human Genetics 2007 122 2 201 206 (Pubitemid 47241785)
Zaba L. C., Surez-Farias M., Fuentes-Duculan J., Nograles K. E., Guttman-Yassky E., Cardinale I., Lowes M. A., Krueger J. G., Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes Journal of Allergy and Clinical Immunology 2009 124 5 1022 1030
Sa S. M., Valdez P. A., Wu J., Jung K., Zhong F., Hall L., Kasman I., Winer J., Modrusan Z., Danilenko D. M., Ouyang W., The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis Journal of Immunology 2007 178 4 2229 2240 (Pubitemid 46233421)
Toichi E., Torres G., McCormick T. S., Chang T., Mascelli M. A., Kauffman C. L., Aria N., Gottlieb A. B., Everitt D. E., Frederick B., Pendley C. E., Cooper K. D., An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL-12/IL-23 in psoriasis Journal of Immunology 2006 177 7 4917 4926 (Pubitemid 44469828)
Jinushi M., Tahara H., Cytokine gene-mediated immunotherapy: current status and future perspectives Cancer Science 2009 100 8 1389 1396
Alonso M. N., Wong M. T., Zhang A. L., Winer D., Suhoski M. M., Tolentino L.L., Gaitan J., Davidson M.G., Kung T.H., Galel D.M., Nadeau K.C., Kim J., Utz P.J., Sderstrm K., Engleman E.G., T(H)1, T(H)2, and T(H)17 cells instruct monocytes to differentiate into specialized dendritic cell subsets Blood 2011 118 3311 3320
Lowes M. A., Kikuchi T., Fuentes-Duculan J., Cardinale I., Zaba L. C., Haider A. S., Bowman E. P., Krueger J. G., Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells Journal of Investigative Dermatology 2008 128 5 1207 1211 (Pubitemid 351543220)
Yao Z., Painter S. L., Fanslow W. C., Ulrich D., Macduff B. M., Spriggs M. K., Armitage R. J., Human IL-17: a novel cytokine derived from T cells Journal of Immunology 1995 155 12 5483 5486
Nograles K. E., Zaba L. C., Guttman-Yassky E., Fuentes-Duculan J., Surez-Farias M., Cardinale I., Khatcherian A., Gonzalez J., Pierson K. C., White T. R., Pensabene C., Coats I., Novitskaya I., Lowes M. A., Krueger J. G., Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways British Journal of Dermatology 2008 159 5 1092 1102
Nograles K. E., Davidovici B., Krueger J. G., New Insights in the Immunologic Basis of Psoriasis Seminars in Cutaneous Medicine and Surgery 2010 29 1 3 9
Duhen T., Geiger R., Jarrossay D., Lanzavecchia A., Sallusto F., Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells Nature Immunology 2009 10 8 857 863
Trifari S., Kaplan C. D., Tran E. H., Crellin N. K., Spits H., Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells Nature Immunology 2009 10 8 864 871
Yawalkar N., Karlen S., Hunger R., Brand C. U., Braathen L. R., Expression of interleukin-12 is increased in psoriatic skin Journal of Investigative Dermatology 1998 111 6 1053 1057 (Pubitemid 29115174)
Lee E., Trepicchio W. L., Oestreicher J. L., Pittman D., Wang F., Chamian F., Dhodapkar M., Krueger J. G., Increased Expression of Interleukin 23 p19 and p40 in Lesional Skin of Patients with Psoriasis Vulgaris Journal of Experimental Medicine 2004 199 1 125 130 (Pubitemid 38076484)
Aggarwal S., Ghilardi N., Xie M. H., De Sauvage F. J., Gurney A. L., Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 Journal of Biological Chemistry 2003 278 3 1910 1914 (Pubitemid 36801431)
Piskin G., Sylva-Steenland R. M. R., Bos J. D., Teunissen M. B. M., In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin Journal of Immunology 2006 176 3 1908 1915 (Pubitemid 43134336)
Yawalkar N., Tscharner G. G., Hunger R. E., Hassan A. S., Increased expression of IL-12p70 and IL-23 by multiple dendritic cell and macrophage subsets in plaque psoriasis Journal of Dermatological Science 2009 54 2 99 105
Luo J., Wu S. J., Lacy E. R., Orlovsky Y., Baker A., Teplyakov A., Obmolova G., Heavner G. A., Richter H. T., Benson J., Structural Basis for the Dual Recognition of IL-12 and IL-23 by Ustekinumab Journal of Molecular Biology 2010 402 5 797 812
Croxtall J. D., Ustekinumab. A review of its use in the management of moderate to severe plaque psoriasis Drugs 2011 71 1733 1753
Kauffman C. L., Aria N., Toichi E., McCormick T. S., Cooper K. D., Gottlieb A. B., Everitt D. E., Frederick B., Zhu Y., Graham M. A., Pendley C. E., Mascelli M. A., A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis Journal of Investigative Dermatology 2004 123 6 1037 1044 (Pubitemid 39586823)
Leonardi C. L., Kimball A. B., Papp K. A., Yeilding N., Guzzo C., Wang Y., Li S., Dooley L. T., Gordon K.B., Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76 week results from a randomized, double-blind, placebo-controlled trial (Phoenix 1) The Lancet 2008 371 1665 1674 (Pubitemid 351671883)
Rallis E., Kintzoglou S., Verros C., Ustekinumab for rapid treatment of nail psoriasis Archives of Dermatology 2010 146 11 1315 1316
Mangan P. R., Harrington L. E., O'Quinn D. B., Helms W. S., Bullard D. C., Elson C. O., Hatton R. D., Wahl S. M., Schoeb T. R., Weaver C. T., Transforming growth factor- induces development of the T H17 lineage Nature 2006 441 7090 231 234
Bettelli E., Carrier Y., Gao W., Korn T., Strom T. B., Oukka M., Weiner H. L., Kuchroo V. K., Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells Nature 2006 441 7090 235 238
McKenzie B. S., Kastelein R. A., Cua D. J., Understanding the IL-23-IL-17 immune pathway Trends in Immunology 2006 27 1 17 23 (Pubitemid 43083560)
Lowes M. A., Bowcock A. M., Krueger J. G., Pathogenesis and therapy of psoriasis Nature 2007 445 7130 866 873
Chen Z., O'Shea J. J., Th17 cells: a new fate for differentiating helper T cells Immunologic Research 2008 41 2 87 102
Kikly K., Liu L., Na S., Sedgwick J. D., The IL-23/Th17 axis: therapeutic targets for autoimmune inflammation Current Opinion in Immunology 2006 18 6 670 675 (Pubitemid 44635178)
Asarch A., Barak O., Loo D. S., Gottlieb A. B., Th17 cells: a new therapeutic target in inflammatory dermatoses Journal of Dermatological Treatment 2008 19 6 318 326
Asarch A., Barak O., Loo D. S., Gottlieb A. B., Th17 cells: a new paradigm for cutaneous inflammation Journal of Dermatological Treatment 2008 19 5 259 266
Komura K., Fujimoto M., Hasegawa M., Ogawa F., Hara T., Muroi E., Takehara K., Sato S., Increased serum interleukin 23 in patients with systemic sclerosis Journal of Rheumatology 2008 35 1 120 125
Larsen J. M., Bonefeld C. M., Poulsen S. S., Geisler C., Skov L., IL-23 and TH17-mediated inflammation in human allergic contact dermatitis Journal of Allergy and Clinical Immunology 2009 123 2 486 492
Zhao Y., Balato A., Fishelevich R., Chapoval A., Mann D. L., Gaspari A. A., Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitis British Journal of Dermatology 2009 161 6 1301 1306
Ryan C., Thrash B., Warren R. B., Menter A., The use of ustekinumab in autoimmune disease Expert Opinion on Biological Therapy 2010 10 4 587 604
Wong C. K., Lit L. C. W., Tam L. S., Li E. K. M., Wong P. T. Y., Lam C. W. K., Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity Clinical Immunology 2008 127 3 385 393
Shah K., Lee W. W., Lee S. H., Kim S. H., Kang S. W., Craft J., Kang I., Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus Arthritis Research and Therapy 2010 12 2, article R53
Kim H. R., Kim H. S., Park M. K., Cho M. L., Lee S. H., Kim H. Y., The clinical role of IL-23p19 in patients with rheumatoid arthritis Scandinavian Journal of Rheumatology 2007 36 4 259 264
Schmidt C., Giese T., Ludwig B., Mueller-Molaian I., Marth T., Zeuzem S., Meuer S. C., Stallmach A., Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis Inflammatory Bowel Diseases 2005 11 1 16 23 (Pubitemid 40340252)
Lew W., Chang J. Y., Jung J. Y., Bang D., Increased expression of interleukin-23 p19 mRNA in erythema nodosum-like lesions of Behet's disease British Journal of Dermatology 2008 158 3 505 511 (Pubitemid 351239193)