HMGB1 Promotes the Differentiation of Th17 via Up-Regulating TLR2 and IL-23 of CD14+Monocytes from Patients with Rheumatoid Arthritis
HMGB1 Promotes the Differentiation of Th17 via Up-Regulating TLR2 and IL-23 of CD14+Monocytes from Patients with Rheumatoid Arthritis
复制标题
HMGB1通过上调类风湿关节炎患者CD14+单核细胞的TLR2和IL-23促进Th17分化
DOI：
10.1111/j.1365-3083.2012.02759.x
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发表时间：
2012-11-01
影响因子：
3.7
通讯作者：
Xu, H.
中科院分区：
文献类型：
--
作者：
He, Z.;Shotorbani, S. S.;Xu, H.
高迁移率族蛋白 1 (HMGB1) 是一种释放到细胞外的非组蛋白核蛋白，与自身免疫性疾病有关。 Toll 样受体 2 (TLR2) 信号传导被认为对于炎症反应和免疫疾病至关重要。最近的研究中，在类风湿性关节炎（RA）中分别发现了 HMGB1 和 TLR2 表达增强。本研究的目的是探讨HMGB1刺激是否可以上调RA患者CD14+单核细胞上TLR2的表达，并阐明涉及Th17细胞和Th17细胞相关细胞因子变化的后续事件。结果显示，与健康对照相比，RA患者外周血单核细胞（PBMC）中CD14+细胞的频率明显升高，CD14+单核细胞上TLR2表达增强，具有统计学意义（P < 0.001）。此外，HMGB1刺激单核细胞后，患者培养单核细胞上清液和患者血浆中IL-17、IL-23和IL-6水平升高，TLR2下游靶标NF-κB也明显升高。这意味着 TLR2 通路和 Th17 细胞极化的增强可能是由于类风湿性关节炎中 HMGB1 的刺激所致。
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 patients plasma were increased, and NF-?B, 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.