HMGB1 Promotes the Differentiation of Th17 via Up-Regulating TLR2 and IL-23 of CD14+ Monocytes from Patients with Rheumatoid Arthritis

Abstract

High-mobility group box 1 (HMGB1) is a non-histone nuclear protein that is released extracellulary and has been implicated in autoimmune disease. Toll-like receptor 2 (TLR2) signalling is thought to be essential for the inflammatory response and for immune disorders. In recent studies, enhanced HMGB1 and TLR2 expressions have been found in rheumatoid arthritis (RA), respectively. The aim of this study is to explore whether HMGB1 stimulation can up-regulate the expression of TLR2 on CD14+ monocytes from patients with RA and to clarify the subsequent events involving Th17 cells and Th17 cell-associated cytokine changes. Our results showed that the frequency of CD14+ cells in peripheral blood mononuclear cell (PBMC) was obviously increased, and enhanced expression of TLR2 on CD14+ monocytes was also found in patients with RA, compared with healthy controls with statistical significance (P<0.001). In addition, the levels of IL-17, IL-23 and IL-6 in supernatants from cultured monocytes from patients and in patient's plasma were increased, and NF-κB, the downstream target of TLR2, also showed a marked elevation after monocytes were stimulated by HMGB1. This implies that the enhanced TLR2 pathway and Th17 cell polarization may be due to HMGB1 stimulation in rheumatoid arthritis. Scandinavian Journal of Immunology. © 2012 Blackwell Publishing Ltd.