Gene delivery of TIPE2 attenuates collagen-induced arthritis by modulating inflammation

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that leads to severe disabilities through the induction of synovitis and subsequent cartilage and bone destruction. The development of a novel therapeutic strategy for suppressing inflammatory responses in RA will be of great benefit to patients. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is an important regulator of immune response in various diseases. However, the expression and function of TIPE2 in RA are still unclear. In the present study, the expression of TIPE2 during the development of collagen-induced arthritis (CIA) was determined. Lentivirus (LV) was utilized to deliver a TIPE2 overexpression system into the joints of CIA mice, and this was followed by pathological analysis, immune cell infiltration analysis, and inflammatory cytokine detection. TIPE2 was downregulated in CIA mice, which was inversely correlated with arthritis progression. The ectopic expression of TIPE2 from gene delivery prevented susceptibility and disease severity by inhibiting the infiltration of macrophages and myeloid-derived suppressor cells (MDSCs) in the joints of CIA mice. Furthermore, lower expression of proinflammatory cytokines was observed in LV-TIPE2-injected CIA mice, which was in part associated with the activation of STAT3 and NF-κB signaling pathways in the cartilage cells. These data support the suppressive function of TIPE2 in autoimmune diseases and identify the gene delivery of TIPE2 as an important therapeutic agent for the treatment of RA and perhaps other autoimmune diseases.