Interleukin-17 in systemic lupus erythematosus: A comprehensive review

Abstract

Systemic lupus erythematosus (SLE) is a complicated autoimmune disease of multifactorial pathoaetiology. One of the most serious manifestations is lupus nephritis. The pathogenesis of SLE has not been well elucidated, but it has been reported that interleukin-17 (IL-17) and Th17 cells play important roles in the pathogenesis of SLE. IL-17A, a member of IL-17 family, amplifies the immune response by inducing the local production of chemokines and cytokines, recruiting neutrophils and monocytes, augmenting the production of autoantibodies, and aggravating the inflammation and damage of target organs such as the kidney in SLE. In recent years, several IL-17A pathway inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibody and the anti-17RA monoclonal antibody. Several agents have shown great success in Phase II trials in multiple autoimmune diseases such as psoriasis, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, and non-infectious uveitis, which has sparked the urgent need of anti-IL-17A as innovative therapeutic option in controlling disease activity of moderate-to-severe SLE. Here, we review and summarize current progress in IL-17A and SLE from in vitro studies, human expression studies, and animal models, providing novel insight into its therapeutic potential.

Oxidative Stress and Treg and Th17 Dysfunction in Systemic Lupus Erythematosus

“…Expansion of Th17 cells has been included in a growing list of autoimmune disorders [53, 54]. Our studies, as well as those of others, have demonstrated that Th17 cells play a key role in the pathogenesis of SLE [17, 18, 54].…”

“…Expansion of Th17 cells has been included in a growing list of autoimmune disorders [53, 54]. Our studies, as well as those of others, have demonstrated that Th17 cells play a key role in the pathogenesis of SLE [17, 18, 54]. Environmental factors, including exposure to UV radiation, infection, environmental pollution, and emotional changes, are believed to contribute to the increased prevalence of SLE and to aggravate lupus activity [55].…”

IL-17A blockade or deficiency does not affect progressive renal fibrosis following renal ischaemia reperfusion injury in mice

“…In recent years, several IL‐17A pathway inhibitors (e.g. brodalumab, ixekizumab and secukinumab) have been tested in clinical trials . More recently, IL‐17‐producing T cells have been shown to induce renal inflammation by activating neutrophils or by participating in macrophage‐mediated tissue injury .…”

“…brodalumab, ixekizumab and secukinumab) have been tested in clinical trials. [5] More recently, IL-17-producing T cells have been shown to induce renal inflammation by activating neutrophils or by participating in macrophagemediated tissue injury. [6] Furthermore, T cells and cytokines participate in proliferative glomerulonephritis as well as ischaemia reperfusion injury (IRI).…”

Progress in interleukin‐2 therapy for rheumatic immune diseases by regulating the immune balance of T cells

“…There are studies have found that the number of Th17 cells and IL‐17 levels significantly increased in SLE patients and SLE mice . IL‐17 has synergistic effect on B cell‐activating factor (BAFF), promotes B cell differentiation and autoantibody production, and induces or promotes SLE . The role of Th17 cells and their cytokines in the pathogenesis of RA has been confirmed in RA rat model and human body.…”