Rheumatoid arthritis: Development after the emergence of a chemokine for neutrophils in the synovium

Abstract

Rheumatoid arthritis (RA) may not be a multifactorial disease; it can be hypothesized that RA is developed through a series of events following a triggering event, which is the emergence of a chemokine for neutrophils in the synovium. IL-17A, secreted by infiltrated neutrophils, stimulates synoviocytes to produce CCL20, which attracts various CCR6-expressing cells, including Th17 cells. Monocytes (macrophages) appear after neutrophil infiltration according to the natural course of inflammation and secrete IL-1β and TNFα. Then, IL-17A, IL-1β, and TNFα stimulate synoviocytes to produce CCL20, amplifying the inflammation. Varieties of chemokines secreted by infiltrating cells accumulate in the synovium and induce synoviocyte proliferation by binding to the corresponding G protein-coupled receptors, thus expanding the synovial tissue. CCL20 in this tissue attracts circulating monocytes that express both CCR6 and receptor activator of NF-κB (RANK), which differentiate into osteoclasts in the presence of RANKL. In this way, pannus is formed, and bone destruction begins.