The IL-17/IL-23 Axis and Its Genetic Contribution to Psoriatic Arthritis

Frontiers in Immunology

Vivien Xanath Hake¹  Matteo Vecellio¹  Carlo Selmi¹  Maria Cristina Carena²  Connor Davidson³  B. Paul Wordsworth³ 

[1] Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, IRCCS, Milan, Italy;Leukocyte Biology Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy;Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom;

关键词: genetics;    psoriatic arthritis;    IL17;    IL23;    SNPs (single nucleotide polymorphisms);    therapy;   

DOI  :  10.3389/fimmu.2020.596086

来源: DOAJ

【 摘 要 】

Psoriatic arthritis (PsA) is a chronic inflammatory disease belonging to the family of spondyloarthropathies (SpA). PsA commonly aggravates psoriasis of the skin and frequently manifests as an oligoarthritis with axial skeletal involvement and extraarticular manifestations including dactylitis, enthesitis, and uveitis. The weight of genetic predisposition to psoriasis and PsA is illustrated by the concordance rates in monozygotic twins which clearly demonstrate that genomics is insufficient to induce the clinical phenotype. The association of PsA with several single nucleotide polymorphisms (SNPs) at the IL23R locus and the involvement of Th17 cells in the immunopathogenesis of PsA clearly put the IL-23/IL-17 axis in the spotlight. The IL-23 and IL-17 cytokines have a pivotal role in the chronic inflammation of the synovium in PsA and are also prominent in the skin lesions of those with PsA. In this review, we focus on the genetic association of the IL-23/IL-17 axis with PsA and the contribution of these master cytokines in the pathophysiology of the disease, highlighting the main cell types incriminated in PsA and their specific role in the peripheral blood, lesional skin and joints of patients. We then provide an overview of the approved biologic drugs targeting the IL-23/IL-17 axis and discuss the advantages of genetic stratification to enhance personalized therapies in PsA.

【 授权许可】

Unknown