TNFAIP3 regulates inflammatory arthritis through the differentiation of monocytes into macrophages.

Abstract

Background: Rheumatoid arthritis (RA) is a disease characterized by synovitis. The synovium of RA patients is rich in macrophages, which are differentiated mainly from monocytes. The susceptibility gene of RA, tumor necrosis factor-α inducible protein 3 (tnfaip3), is considered an anti-inflammatory factor. Our previous study revealed the abnormal protein expression of TNFAIP3 in monocytes from patients with RA.

Objective: In the present study, we aimed to explore the role of TNFAIP3 in monocytes in RA and its potential functions.

Methods: In vivo, we injected adenoviral vectors overexpressing tnfaip3 into mice with collagen-induced arthritis (CIA) (the TNFAIP3-oe group). Arthritis scores, as well as the expression of iNOS and CD206 in the synovium, were compared between the TNFAIP3-oe group and the CIA group. In vitro, we used lentivirus transfection to upregulate/downregulate the expression of tnfaip3 in THP-1 cells. The ability of these cells to migrate, secrete cytokines and differentiate into macrophages was compared.

Results: Compared with that in the CIA group, arthritis in the TNFAIP3-oe group was ameliorated (p = 0.030). Moreover, the joints of these mice presented more CD206+ cells and fewer iNOS+ cells (both p < 0.001), indicating the anti-inflammatory effect of TNFAIP3 and its regulation of macrophage polarization. In vitro, the tnfaip3-depleted cells (the TNFAIP3-i group) had greater migration and differentiated into M1 macrophages, and more cells overexpressing tnfaip3 (the TNFAIP3-oe group) differentiated into M2 macrophages. Furthermore, cells in the TNFAIP3-i group showed increased secretion of the proinflammatory cytokines IL-6 and MMPs.

Conclusions: Taken together, these findings suggest that TNFAIP3 in monocytes can regulate inflammatory arthritis by modulating monocyte migration, differentiation, and cytokine secretion.