Role of IL-17 in Psoriasis and Psoriatic Arthritis

Overview

Journal Clin Rev Allergy Immunol

Specialty Allergy & Immunology

Date 2012 Feb 25

PMID 22362575

Citations 63

Authors

Siba P Raychaudhuri

Affiliations

Soon will be listed here.

Abstract

The role of T cell subpopulations in human disease is in a transition phase due to continuous discovery of new subsets of T cell, one of which is Th17, characterized by the production of signature cytokine IL-17. In the last couple of years, many articles are coming out on the role of Th17 and its signature cytokine IL-17 in different autoimmune diseases like rheumatoid arthritis, psoriasis, psoriatic arthritis (PsA), SLE and multiple sclerosis. Psoriasis and PsA are immune-mediated diseases, affecting the skin and joints, respectively. Initially, it was thought that psoriasis and PsA were Th1-mediated diseases; however, studies in knockout animal models (IL-17 knockout mice) as well as human experimental data indicate that Th17 and its signature cytokine IL-17 have a critical role in the pathogenesis of psoriatic disease. Th17 cells have been identified from the dermal extracts of psoriatic lesions. Subsequently, our research group has substantiated this observation that Th17 cells are enriched in the papillary dermis of psoriatic plaques and in freshly isolated effector T lymphocytes from the synovial fluid of PsA patients, and we have reported that the majority of these CD4 + IL-17+ T cells are of memory phenotype (CD4RO(+)CD45RA(-)CD11a(+)). Recent reports also suggest that the synovial tissue in psoriatic arthritis is enriched with IL-17R, and its most well recognized receptor IL-17RA is functionally active in psoriatic arthritis. In this review article, we have discussed the role of IL-17 in psoriatic disease and have narrated about the novel IL17/IL-17R antibodies currently in preparation for its therapeutic uses in autoimmune diseases.

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References

Raychaudhuri S, Kundu-Raychaudhuri S, Tamura K, Masunaga T, Kubo K, Hanaoka K . FR255734, a humanized, Fc-Silent, Anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model. J Invest Dermatol. 2008; 128(8):1969-76. DOI: 10.1038/jid.2008.38. View

Koshy P, Henderson N, Logan C, Life P, Cawston T, Rowan A . Interleukin 17 induces cartilage collagen breakdown: novel synergistic effects in combination with proinflammatory cytokines. Ann Rheum Dis. 2002; 61(8):704-13. PMC: 1754191. DOI: 10.1136/ard.61.8.704. View

Zaba L, Cardinale I, Gilleaudeau P, Sullivan-Whalen M, Suarez-Farinas M, Suarez Farinas M . Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med. 2007; 204(13):3183-94. PMC: 2150965. DOI: 10.1084/jem.20071094. View

Evans H, Suddason T, Jackson I, Taams L, Lord G . Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes. Proc Natl Acad Sci U S A. 2007; 104(43):17034-9. PMC: 2040448. DOI: 10.1073/pnas.0708426104. View

van Hamburg J, Mus A, de Bruijn M, de Vogel L, Boon L, Cornelissen F . GATA-3 protects against severe joint inflammation and bone erosion and reduces differentiation of Th17 cells during experimental arthritis. Arthritis Rheum. 2009; 60(3):750-9. DOI: 10.1002/art.24329. View

Krueger G, Langley R, Leonardi C, Yeilding N, Guzzo C, Wang Y . A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med. 2007; 356(6):580-92. DOI: 10.1056/NEJMoa062382. View

Bettelli E, Carrier Y, Gao W, Korn T, Strom T, Oukka M . Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006; 441(7090):235-8. DOI: 10.1038/nature04753. View

Veldhoen M, Hocking R, Atkins C, Locksley R, Stockinger B . TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity. 2006; 24(2):179-89. DOI: 10.1016/j.immuni.2006.01.001. View

Nestle F, Kaplan D, Barker J . Psoriasis. N Engl J Med. 2009; 361(5):496-509. DOI: 10.1056/NEJMra0804595. View

10.

Canete J, Martinez S, Farres J, Sanmarti R, Blay M, Gomez A . Differential Th1/Th2 cytokine patterns in chronic arthritis: interferon gamma is highly expressed in synovium of rheumatoid arthritis compared with seronegative spondyloarthropathies. Ann Rheum Dis. 2000; 59(4):263-8. PMC: 1753106. DOI: 10.1136/ard.59.4.263. View

11.

Kramer J, Hanel W, Shen F, Isik N, Malone J, Maitra A . Cutting edge: identification of a pre-ligand assembly domain (PLAD) and ligand binding site in the IL-17 receptor. J Immunol. 2007; 179(10):6379-83. PMC: 2973996. DOI: 10.4049/jimmunol.179.10.6379. View

12.

Nakae S, Iwakura Y, Suto H, Galli S . Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17. J Leukoc Biol. 2007; 81(5):1258-68. DOI: 10.1189/jlb.1006610. View

13.

Ziolkowska M, Koc A, Luszczykiewicz G, Ksiezopolska-Pietrzak K, Klimczak E, Chwalinska-Sadowska H . High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J Immunol. 2000; 164(5):2832-8. DOI: 10.4049/jimmunol.164.5.2832. View

14.

Griffiths C, Barker J . Pathogenesis and clinical features of psoriasis. Lancet. 2007; 370(9583):263-271. DOI: 10.1016/S0140-6736(07)61128-3. View

15.

Bush K, Farmer K, Walker J, Kirkham B . Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum. 2002; 46(3):802-5. DOI: 10.1002/art.10173. View

16.

Notley C, Inglis J, Alzabin S, McCann F, McNamee K, Williams R . Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells. J Exp Med. 2008; 205(11):2491-7. PMC: 2571924. DOI: 10.1084/jem.20072707. View

17.

Colin E, Asmawidjaja P, van Hamburg J, Mus A, van Driel M, Hazes J . 1,25-dihydroxyvitamin D3 modulates Th17 polarization and interleukin-22 expression by memory T cells from patients with early rheumatoid arthritis. Arthritis Rheum. 2009; 62(1):132-42. DOI: 10.1002/art.25043. View

18.

Villadsen L, Schuurman J, Beurskens F, Dam T, Dagnaes-Hansen F, Skov L . Resolution of psoriasis upon blockade of IL-15 biological activity in a xenograft mouse model. J Clin Invest. 2003; 112(10):1571-80. PMC: 259129. DOI: 10.1172/JCI18986. View

19.

Torti D, Feldman S . Interleukin-12, interleukin-23, and psoriasis: current prospects. J Am Acad Dermatol. 2007; 57(6):1059-68. DOI: 10.1016/j.jaad.2007.07.016. View

20.

Jandus C, Bioley G, Rivals J, Dudler J, Speiser D, Romero P . Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008; 58(8):2307-17. DOI: 10.1002/art.23655. View