Abstract

The angiogenic factors angiopoietin (Ang)-1 and Ang-2, and their shared receptor Tie2, are expressed in rheumatoid arthritis (RA) synovial tissue. Clinical and translational studies have suggested important roles for Ang-1, Ang-2 and Tie2 in the pathology of RA, but the cellular targets of Ang signalling and the specific contributions of Ang-1 and Ang-2 to disease are poorly understood. Here, I discuss recent findings that synovial macrophages are prominent targets of Ang signalling, highlighting the distinct contributions that Ang-1 and Ang-2 make to macrophage activation, the role of macrophage polarization in regulating Tie2 expression and signalling, and evidence that engagement of synovial Tie2 by Ang-1 drives the development of persistent erosive RA in early arthritis patients. Together, these studies suggest a previously unappreciated role for angiogenic macrophage Tie2 signalling in promoting the initiation and persistence of pathology in RA.