Ramos Maria Ines, Garcia Samuel, Helder Boy, Aarrass Saida, Reedquist Kris A, Jacobsen Sten E, Tak Paul Peter, Lebre Maria Cristina
Department of Clinical Immunology and Rheumatology.
Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
J Transl Autoimmun. 2020 Sep 16;3:100066. doi: 10.1016/j.jtauto.2020.100066. eCollection 2020.
Rheumatoid arthritis (RA) is chronic autoimmune disease which etiology remains unknown. Several cell types have been described to potentiate/aggravate the arthritic process however the initiating event in synovial inflammation is still elusive. Dendritic cells (DCs) are essential for the initiation of primary immune responses and thus we hypothesized that these cells might be crucial for RA induction. DCs are a heterogeneous population of cells comprising different subsets with distinct phenotype and function. Here we investigated which DC subset(s) is/are crucial for the initiation of the arthritic process. We have previously demonstrated that Flt3-/- mice, with reduced DCs, were protected from collagen induced arthritis (CIA). Here we have shown that GM-CSF derived DCs in Flt3L-/- mice are functional but not sufficient to induce arthritis. Batf3 mice lacking both CD103 and CD8α cDC1 were resistant to collagen induced arthritis (CIA), demonstrating that this DC subset is crucial for arthritis development. CEP-701 (a Flt3L inhibitor) treatment prevented CIA induction, and reduced dramatically the numbers CD103 cDC1s present in the lymph nodes and synovium. Hence this study identified cDC1 as the main subset orchestrating the initiation of cell-mediated immunity in arthritis.
类风湿性关节炎（RA）是一种病因不明的慢性自身免疫性疾病。已有多种细胞类型被描述为可增强/加重关节炎进程，然而滑膜炎症的起始事件仍不清楚。树突状细胞（DCs）对于启动原发性免疫反应至关重要，因此我们推测这些细胞可能对RA的诱导起关键作用。DCs是一群异质性细胞，由具有不同表型和功能的不同亚群组成。在这里，我们研究了哪些DC亚群对关节炎进程的启动至关重要。我们之前已经证明，DCs数量减少的Flt3-/-小鼠对胶原诱导的关节炎（CIA）具有抵抗力。在这里，我们已经表明，Flt3L-/-小鼠中由粒细胞-巨噬细胞集落刺激因子（GM-CSF）衍生的DCs具有功能，但不足以诱导关节炎。缺乏CD103和CD8α cDC1的Batf3小鼠对胶原诱导的关节炎（CIA）具有抗性，表明该DC亚群对关节炎发展至关重要。CEP-701（一种Flt3L抑制剂）治疗可预防CIA的诱导，并显著减少淋巴结和滑膜中CD103 cDC1的数量。因此，本研究确定cDC1是在关节炎中协调细胞介导免疫启动的主要亚群。
