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

Matteo Vecellio,Carlo Selmi,Connor Davidson,B Paul Wordsworth,Vivien Xanath Hake,Maria Cristina Carena

doi:10.3389/fimmu.2020.596086

Abstract

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.

Highlights

Psoriatic arthritis (PsA) is a common inflammatory disease affecting the joints and it is usually accompanied by plaque psoriasis (Ps) [1]
The contribution of the IL-23/IL-17 axis to the development of PsA will be discussed highlighting Th-17 biology and the production of a pro-inflammatory milieu in the skin and in the synovium, and how this leads to the activation of osteoclasts, which are responsible for bone degradation, and of keratinocytes and neutrophils, which are implicated in the epidermal hyperplasia
PsA is a complex polygenic disease with a genetic contribution that overlaps with other related conditions such as psoriasis, ankylosing spondylitis (AS) and IBD

Summary

Introduction

Psoriatic arthritis (PsA) is a common inflammatory disease affecting the joints and it is usually accompanied by plaque psoriasis (Ps) [1]. PsA is a polygenic immune-mediated disease: genome-wide association studies (GWAS) have identified many genes/ genomic loci increasing susceptibility for PsA, many of which are common to psoriasis uncomplicated by arthritis; these include HLA-A, HLA-B, HLA-C, IL23R, CSF2 (Colony Stimulating Factor 2 or granulocyte-macrophage colony stimulating factor), TRAF3IP2 (TRAF3 Interacting Protein 2), NOS2 (Nitric Oxide Synthase 2) [31, 32].

Results

Conclusion