Despite a ballooning therapeutic tool box, treatment responses to newer biologic agents and oral small molecules in psoriatic arthritis (PsA) and spondyloarthritis (SpA) are of similar magnitude to those observed with anti-Tumor Necrosis Factor (TNF) medications (1, 2).The PsA and SpA therapeutic outcomes stand in marked contrast to those reported in psoriasis where blockade of molecules in the IL-23/IL-17 pathway often provide prolonged, deep responses and in some cases even remission (3).
IL-17A blockade was performed in HLA-B27/human β<sub>2</sub> -microglobulin (hβ<sub>2</sub> m)-transgenic rats, which served as a model for SpA in both prophylactic and therapeutic settings.
Murine models of interleukin (IL)-23-driven spondyloarthritis (SpA) have demonstrated entheseal accumulation of γδT-cells which were responsible for the majority of local IL-17A production.
Nevertheless, a number of knowledge gaps exist regarding the role of IL-17A in the pathophysiology of spondyloarthritis in man, including its cellular origin, its precise role in discrete disease processes such enthesitis, bone erosion, and bone formation, and the reasons for the discrepant responses to IL-17A inhibition observed in certain other spondyloarthritis manifestations.
Translational data in humans have demonstrated an increase in the number of ILC3s responsive to IL-23 and producing either IL-22 or IL-17 in the gut of SpA patients.
Spondyloarthritis (SpA), a chronic inflammatory, rheumatic disease, and hidradenitis suppurativa (HS), a chronic, debilitating, inflammatory skin disease, share several clinical and pathophysiological features, such as the association with inflammatory bowel disease and elevated cytokine levels IL-17 and TNF-α.
IL-7 is a cytokine whose ability to stimulate IL-17 production in both innate and adaptive immunity cells has made it a promising target not only for a better understanding of the disease as well as an important potential therapeutic target in patients with SpA.
Cytokines from the IL-17 family have been shown to be involved in the pathogenesis of several diseases such as spondyloarthritis, psoriatic arthritis, or psoriasis.
This study was undertaken to characterize the presence and composition of ILCs, and investigate whether these cells are an important source of IL-17A, in the synovial tissue (ST) of patients with SpA.
Clinical improvement in joint counts was associated with a histologic decrease in synovial sublining macrophages (P = 0.028) and neutrophils (P = 0.004), both of which are sensitive synovial biomarkers of inflammatory response in peripheral SpA, as well as with decreased synovial expression of IL-17A messenger RNA (mRNA) (P = 0.010) but not of tumor necrosis factor mRNA.
In this review, we will examine key preclinical studies that demonstrated the mechanistic role of IL-17A in the development SpA and discuss how these observations were translated into clinical practice.
Targeted Delivery of the HLA-B<sup>∗</sup>27-Binding Peptide into the Endoplasmic Reticulum Suppresses the IL-23/IL-17 Axis of Immune Cells in Spondylarthritis.
Knowledge regarding the mechanisms of the IL17-IL23 pathway and its role in spondyloarthritis (SpA) has been pivotal to the development of IL-17 blockade in patients with axial SpA.