Interleukin-7 induced immunopathology in arthritis

Interleukin (IL)-7 is a potent immunoregulatory cytokine that is detected in joints of patients with rheumatoid and juvenile idiopathic arthritis and which correlates with parameters of disease. Several synovial cell types that play an important role in inflammation and immunopathology, such as macrophages, dendritic cells, and fibroblasts, produce IL-7. IL-7 induces cytokines produced by arthritogenic T cells (for example, interferon gamma (IFNgamma), IL-17), T cell differentiating factors (for example, IL-12), chemokines capable of attracting inflammatory cells (for example, macrophage induced gene (MIG), macrophage inflammatory protein (MIP)-1alpha) as well as molecules involved in cell adhesion, migration, and costimulation (for example, lymphocyte function associated antigen (LFA)-1, CD40, CD80). In addition, IL-7 can induce bone loss by stimulating osteoclastogenesis that is dependent on receptor activator of nuclear factor kappaB ligand (RANKL). IL-7 induces tumour necrosis factor alpha (TNFalpha) secretion by T cells and by monocytes after T cell dependent monocyte/macrophage activation. Importantly, induction of both IL-7 and IL-7 induced effects seems to be able to operate independent of TNFalpha. Together this suggests that IL-7 is an important cytokine in several rheumatic conditions, capable of inducing inflammation and immunopathology. Thus it may be an important target for immunotherapy.