title: The IL-23/IL-17 axis in psoriatic arthritis.
abstract: Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory disease, affecting both the skin and joints. Disease progression is associated with aberrant cytokine expression, and TNF blockade is the most successful therapy to date. However, not all patients are responsive to anti-TNF treatment, highlighting the need to better understand the cellular and molecular mechanisms that govern the disease. PsA associations with single nucleotide polymorphisms in IL23R as well as TRAF3IP2 (Act1), a molecule downstream of the IL-17 receptor (IL-17R), have linked the IL-23/IL-17 axis to disease pathology. Although both cytokines are implicated in PsA, a full picture of their cellular targets and pathogenic mechanisms has not yet emerged. In this review, we focus on the IL-23/IL-17 axis-elicited responses mediated by osteoclasts, keratinocytes and neutrophils. Expanding our understanding of the cellular and molecular mechanisms that dictate pathogenicity in PsA will contribute to developing novel treatment strategies to combat disease.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA 95616, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Divisions of Human Gene Therapy and Pediatric Rheumatology, Program in Immunology, Stanford University, Palo Alto, CA 94305, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Mellins
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA 95616, USA.
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, United Kingdom.
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA 95616, USA; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, CA 95817, USA. Electronic address: iannis@ucdavis.edu.
authors.forename: Iannis E
authors.initials: IE
authors.lastname: Adamopoulos
mesh_terms: D000818:Animals; D015535:Arthritis, Psoriatic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010010:Osteoclasts / Q000276:immunology; D053245:RANK Ligand / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D053245:RANK Ligand
keywords: IL-17; IL-23; NF-κB; Psoriatic arthritis