Department of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
Department of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
Int Immunopharmacol. 2018 Dec;65:348-359. doi: 10.1016/j.intimp.2018.10.016. Epub 2018 Oct 23.
Rheumatoid arthritis (RA) is a chronic systemic, autoimmune and inflammatory disease represented as synovitis, pannus formation, adjacent bone erosions, and joint destruction. The major cells involved in the perpetuation of RA pathogenesis are CD4 T-cells (mainly Th1 cells and Th17 cells), fibroblasts like synoviocytes (FLS), macrophages and B cells. Other autoimmune cells such as dendritic cells, neutrophils, mast cells, and monocytes also contribute to RA pathogenesis. Monocytes are mainly bone marrow (BM) derived cells in the circulation. The chemokine receptors CCR2 and CX3CR1 expressed by monocytes interact with chemokine ligands CCL2 (MCP-1) and CX3CL1 (fractalkine) respectively produced by FLS and this interaction promotes their migration and recruitment into RA synovium. Activated monocytes on their surface exhibit upregulated antigenic expressions such as CD14, CD16, HLA-DR, toll-like receptors (TLRs), and adhesion molecules B1 and B2 integrins. RA monocytes interconnect with other cells in a positive loop manner in the propagation of the rheumatoid process. They skew towards mainly intermediate monocyte subsets (CD14 CD16) which produce proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. Moreover, the predominant intermediate monocytes in RA differentiate into M1-macrophages which play a major role in synovial inflammation. Demonstrations suggest monocytes with CD14 and CD16 expression (classical monocytes?) differentiate to osteoclasts which are the cells responsible for bone erosion in RA synovial joints. Th17 cells induce the production of RANKL by FLS which promotes osteoclastogenesis. Cytokines mainly TNF-α, IL-1β, and IL-6 amplify osteoclastogenesis. Hence, monocytes are the circulating precursors of macrophages and osteoclasts in RA. AIM OF THE REVIEW: To enlighten the identity of monocytes, the antigenic expression on monocyte surface and their cytokines role in RA. We also emphasize about the chemokine receptors expressed by monocytes subsets and chemotaxis of circulating monocytes into RA synovium. Additionally, we review monocytes as the circulating precursors of macrophages and osteoclasts in RA joints and their heterogeneity and plasticity role in RA.
类风湿关节炎（RA）是一种慢性系统性、自身免疫性和炎症性疾病，表现为滑膜炎、血管翳形成、邻近骨侵蚀和关节破坏。参与 RA 发病机制持续的主要细胞是 CD4 T 细胞（主要是 Th1 细胞和 Th17 细胞）、成纤维细胞样滑膜细胞（FLS）、巨噬细胞和 B 细胞。其他自身免疫细胞，如树突状细胞、中性粒细胞、肥大细胞和单核细胞，也有助于 RA 的发病机制。单核细胞主要是循环中的骨髓（BM）来源细胞。单核细胞表达的趋化因子受体 CCR2 和 CX3CR1 分别与 FLS 产生的趋化因子配体 CCL2（MCP-1）和 CX3CL1（ fractalkine）相互作用，促进其迁移和募集到 RA 滑膜中。表面上激活的单核细胞表现出上调的抗原表达，如 CD14、CD16、HLA-DR、Toll 样受体（TLRs）和黏附分子 B1 和 B2 整合素。RA 单核细胞在类风湿过程的传播中以正反馈环的方式与其他细胞相互作用。它们偏向于主要的中间单核细胞亚群（CD14 CD16），这些细胞产生促炎细胞因子，如 TNF-α、IL-1β 和 IL-6。此外，RA 中的主要中间单核细胞分化为 M1 巨噬细胞，在滑膜炎症中起主要作用。研究表明，表达 CD14 和 CD16 的单核细胞（经典单核细胞？）分化为破骨细胞，破骨细胞是 RA 滑膜关节中负责骨侵蚀的细胞。Th17 细胞诱导 FLS 产生 RANKL，促进破骨细胞生成。细胞因子主要是 TNF-α、IL-1β 和 IL-6，放大破骨细胞生成。因此，单核细胞是 RA 中巨噬细胞和破骨细胞的循环前体细胞。综述目的：阐明单核细胞的特性、单核细胞表面的抗原表达及其在 RA 中的细胞因子作用。我们还强调了单核细胞亚群表达的趋化因子受体和循环单核细胞向 RA 滑膜的趋化作用。此外，我们回顾了单核细胞作为 RA 关节中巨噬细胞和破骨细胞的循环前体细胞及其在 RA 中的异质性和可塑性作用。
