IL-17 in Rheumatoid Arthritis and Precision Medicine: From Synovitis Expression to Circulating Bioactive Levels

Abstract

Interleukin (IL)-17A has a direct contribution in early induction and late chronic stages of various inflammatory diseases. In vitro and in vivo experiments have first characterized its local effects on different cell types and then its systemic effects. For instance, IL-17 axis is now identified as a key driver of psoriasis through its effects on keratinocytes. Similar observations apply for rheumatoid arthritis (RA) where IL-17A triggers changes in the synovium that lead to synovitis and maintain local inflammation. These results have prompted the development of biologics to target this cytokine. However, while convincing studies are reported on the efficacy of IL-17 inhibitors in psoriasis, there are conflicting results in RA. Patient heterogeneity but also the involvement of mediators that regulate IL-17 function may explain these results. Therefore, new tools and concepts are required to identify patients that could benefit from these IL-17 targeted therapies in RA and the development of predictive biomarkers of response has started with the emergence of various bioassays. Current strategies are also focusing on synovial biopsies that may be used to stratify patients. From local to systemic levels, new approaches are developing and move the field of RA management into the era of precision medicine.

Association between the polymorphism of IL-17A and IL-17F gene with knee osteoarthritis risk: a meta-analysis based on case-control studies

“…Recent studies have suggested that knee OA might be considered a chronic inflammatory disorder, elevated levels of IL-1, IL-6, IL-17,TNF-α, and other acute-phase proteins that are found in patients with cartilage degradation [25]. A kind of conventional viewpoint is that inflammatory mechanism plays a crucial role in the pathogenesis and evolution of cartilage degeneration and expression of inflammatory reaction [26][27][28]. IL-17 is one of the most important regulators of innate and adaptive immune responses, and it is expressed in synovial tissues, and could contribute to cartilage degeneration and synovial infiltration in joint by inducing the release of chemokines by chondrocytes [29,30].…”

Fighting the storm: novel anti- TNFα and anti-IL-6 C. sativa lines to tame cytokine storm in COVID-19

“…Extracts #4, #6, #8, #13 and #14 down-regulated, while extract #12 upregulated IL-23A, a member of the IL-12 family of cytokines with pro-in ammatory properties 19 . Extracts #8 and #13 downregulated IL-17C, a pro-in ammatory cytokine and a member of IL-17 family, that, together with IL-23 mediates in ammation in psoriasis, psoriatic arthritis, and ankylosing spondylitis 20 . Increased expression of IL-23/IL-17 pathway was previously correlated with pulmonary in ammation in polymicrobial sepsis 21 .…”

Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

“…IL-17A produced by Th17 cells promotes both the production of the pro-inflammatory cytokines IL-6, IL-8, and GM-CSF from epithelial, endothelial, and fibroblastic cells [68] and neutrophil recruitment [69], which leads to local inflammation and promotes disease progression. By these actions, IL-17A contributes to bone erosion, cartilage destruction, and neoangiogenesis in RA patients [70]. IL-17A triggers differentiation of osteoclast progenitors into mature osteoclasts and promotes RANK-L production by osteoblasts and synoviocytes, resulting in both reduced bone formation and enhanced bone erosion [71][72][73].…”