The immunopathogenesis of fibrosis in systemic sclerosis

Abstract

Systemic sclerosis (SSc) is an idiopathic systemic autoimmune disease. It is characterized by a triad of hallmarks: immune dysfunction, fibrosis and vasculopathy. Immune dysfunction in SSc is characterized by the activation and recruitment of immune cells and the production of autoantibodies and cytokines. How immune abnormalities link the fibrosis and vasculopathy in SSc is poorly understood. A plethora of immune cell types are implicated in the immunopathogenesis of SSc, including T cells, B cells, dendritic cells, mast cells and macrophages. How these different cell types interact to contribute to SSc is complicated, and can involve cell-to-cell interactions and communication via cytokines, including transforming growth factor (TGF)-β, interleukin (IL)-6 and IL-4. We will attempt to review significant and recent research demonstrating the importance of immune cell regulation in the immunopathogenesis of SSc with a particular focus on fibrosis.

Keywords: B cells; T cells; Toll-like receptors (TLRs); arthritis (including rheumatoid arthritis).

Figure 1

Potential roles for macrophages in the immunopathogenesis of SSc. (1) Macrophages can both be activated by and release cytokines. Cytokines and chemokines released by macrophages may recruit and activate other immune cells to further promote an inflammatory environment. (2) Internal molecules released from damaged endothelial cells can activate macrophages by Toll‐like receptors (TLRs). (3) Activation of macrophages leads to the secretion of profibrotic molecules and the activation of fibroblasts resulting in fibrosis.