Neutrophil Function in an Inflammatory Milieu of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by the presence of autoantibodies against citrullinated protein antigens and proinflammatory cytokines which cause chronic synovitis, bone erosion, and eventual deformity; however, the precise etiology of RA is unclear. In the early stage of RA, neutrophils migrate into the articular cavity, become activated, and exert their function in an inflammatory process, suggesting an essential role of neutrophils in the initial events contributing to the pathogenesis of RA. Solid evidence exists that supports the contribution of neutrophil extracellular traps (NETs) to the production of autoantibodies against citrullinated proteins which can trigger the immune reaction in RA. Concurrently, proinflammatory cytokines regulate the neutrophil migration, apoptosis, and NET formation. As a result, the inflammatory neutrophils produce more cytokines and influence other immune cells thereby perpetuating the inflammatory condition in RA. In this review, we summarize the advances made in improving our understanding of neutrophil migration, apoptosis, and NET formation in the presence of an RA inflammatory milieu. We will also discuss the most recent strategies in modulating the inflammatory microenvironment that have an impact on neutrophil function which may provide alternative novel therapies for RA.

The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis

“…Currently, serveral studies indicated that multiple immune cells were involved in the development of arthritis. For example, neutrophil could be enrolled in the site of inflammation and play an important role in the disease [11]. In RA patients, 90% of cells in the synovial fluid are neutrophils [19].…”

“…The changes in immune cells after C.sinensis infection in CIA mice Current studies indicated that neutrophils, monocytes, T cells, and B cells, can be attracted and quickly recruited into the sites of infection, and play essential roles in rheumatoid arthritis [11,12]. In the study, we assessed whether C.sinensis infection could affect these immune cells in CIA mice.…”

NETs analysed by novel calprotectin‐based assays in blood donors and patients with multiple myeloma or rheumatoid arthritis: A pilot study

“…Increased NET formation is observed in autoimmune diseases such as systemic lupus erythematosus and RA, where NETs can contribute to autoimmunity by exposing autoantigens, stimulating the inflammasome and activating complement . NETs contribute to the production of autoantibodies against citrullinated proteins in RA . NET release from neutrophils is emerging as an important factor in thrombogenesis, so‐called immunothrombosis, which takes place in sepsis (ie disseminated intravascular coagulation) and malignancy .…”

The Central Role of Acute Phase Proteins in Rheumatoid Arthritis: Involvement in Disease Autoimmunity, Inflammatory Responses, and the Heightened Risk of Cardiovascular Disease

“…The presence of hyperactive neutrophils in RA synovial fluid and pannus tissue, in particular NETosis (formation of neutrophil extracellular traps or NETs), has been confirmed by multiple studies. [198][199][200] NETs are chromatin-derived extracellular snares that are externalized from neutrophils in response to microbial infections or inflammation. 201 Neutrophils and NETosis are key components in the perpetual inflammatory response encountered in RA patients.…”