CD14(+)CD16(-) monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK.
CD14(+)CD16(-) monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK.
复制标题
CD14 CD16 - 单核细胞通过表达 Tyro3TK 成为类风湿关节炎中破骨细胞的主要前体
DOI：
10.1186/s13075-020-02308-7
复制
发表时间：
2020-09-21
影响因子：
4.9
通讯作者：
Su Y
中科院分区：
文献类型：
--
作者：
Xue J;Xu L;Zhu H;Bai M;Li X;Zhao Z;Zhong H;Cheng G;Li X;Hu F;Su Y
单核细胞作为类风湿性关节炎（RA）破骨细胞的前体已经得到了很好的证实，而单核细胞亚群在破骨细胞形成中的作用仍然存在争议。Tyro3酪氨酸激酶（Tyro3TK）是受体酪氨酸激酶家族的一员，参与免疫稳态，其在破骨细胞分化中的作用最近被报道。本研究旨在比较RA中CD14+CD16+和CD14+CD16 -单核细胞的破骨能力，并确定Tyro3TK在其破骨细胞发生中的潜在参与。从健康对照（HC）和RA患者分离的CD14+CD16+和CD14+CD16−单核细胞亚群体外诱导破骨细胞，并通过抗酒石酸酸性磷酸酶（TRAP）染色评估。采用流式细胞术和qPCR技术检测RA、OA、HC患者外周血CD14+CD16+、CD14+CD16−单核细胞亚群中Tyro3TK的表达情况，并分析其与RA患者临床及免疫学特征的相关性。通过阻断Tyro3TK的破骨细胞分化实验，进一步研究Tyro3TK在CD14+CD16−单核细胞介导的破骨细胞发生中的作用。结果显示，CD14+CD16−单核细胞是破骨细胞的主要来源。与HC和OA患者相比，RA患者CD14+CD16−单核细胞上Tyro3TK的表达明显上调，并与IgM水平、压痛关节计数、疾病活动度评分等疾病表现呈正相关。此外，抗tyro3tk抗体能够以剂量依赖的方式抑制gas6介导的CD14+CD16 -单核细胞的破骨细胞分化。这些发现表明，CD14+CD16 -单核细胞上Tyro3TK的升高是RA中破骨细胞分化的关键信号。
Monocytes as precursors of osteoclasts in rheumatoid arthritis (RA) are well demonstrated, while monocyte subsets in osteoclast formation are still controversial. Tyro3 tyrosine kinase (Tyro3TK) is a member of the receptor tyrosine kinase family involved in immune homeostasis, the role of which in osteoclast differentiation was reported recently. This study aimed to compare the osteoclastic capacity of CD14+CD16+ and CD14+CD16− monocytes in RA and determine the potential involvement of Tyro3TK in their osteoclastogenesis. Osteoclasts were induced from CD14+CD16+ and CD14+CD16− monocyte subsets isolated from healthy control (HC) and RA patients in vitro and evaluated by tartrate-resistant acid phosphatase (TRAP) staining. Then, the expression of Tyro3TK on CD14+CD16+ and CD14+CD16− monocyte subsets in the peripheral blood of RA, osteoarthritis (OA) patients, and HC were evaluated by flow cytometry and qPCR, and their correlation with RA patient clinical and immunological features was analyzed. The role of Tyro3TK in CD14+CD16− monocyte-mediated osteoclastogenesis was further investigated by osteoclast differentiation assay with Tyro3TK blockade. The results revealed that CD14+CD16− monocytes were the primary source of osteoclasts. Compared with HC and OA patients, the expression of Tyro3TK on CD14+CD16− monocytes in RA patients was significantly upregulated and positively correlated with the disease manifestations, such as IgM level, tender joint count, and the disease activity score. Moreover, anti-Tyro3TK antibody could inhibit Gas6-mediated osteoclast differentiation from CD14+CD16− monocytes in a dose-dependent manner. These findings indicate that elevated Tyro3TK on CD14+CD16− monocytes serves as a critical signal for osteoclast differentiation in RA.
登录
查看更多内容
影响因子：
2.2
作者：
Kawaguchi, Hiroshi;Katagiri, Mika;Chikazu, Daichi
通讯作者：
Chikazu, Daichi
影响因子：
4.9
作者：
Komano Y;Nanki T;Hayashida K;Taniguchi K;Miyasaka N
通讯作者：
Miyasaka N
影响因子：
10.1
作者：
Noll, Jacqueline E.;Williams, Sharon A.;Zannettino, Andrew C. W.
通讯作者：
Zannettino, Andrew C. W.
影响因子：
5.2
作者：
Nakamura, YS;Hakeda, Y;Suda, T
通讯作者：
Suda, T
影响因子：
4.9
作者：
Lari R;Kitchener PD;Hamilton JA
通讯作者：
Hamilton JA