Laboratory of Innate Immunology, Centre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada.
Division of Rheumatology, CHU de Québec-Université Laval (CHUL), Infectious and Immune Diseases, Centre de recherche du CHU de Québec-Université Laval (CHUL), Québec, QC, Canada.
Eur J Immunol. 2016 Dec;46(12):2789-2800. doi: 10.1002/eji.201646406. Epub 2016 Oct 18.
Monocytes are central to the physiopathology of arthritis, but their roles in progression and resolution of the disease remain to be clarified. Using NR4A1 mice, which lack patrolling lymphocyte antigen 6C (Ly6C ) monocytes, we found that inflammatory Ly6C monocytes contribute to rapid development of arthritis in a serum transfer-induced arthritis (STIA) model. Our experiments suggest that patrolling monocytes do not promote the initiation and progression of arthritis in mice, as severity of symptoms was amplified in NR4A1 mice. Moreover, we show that treatment of arthritic wild type (WT) mice with cytosporone B (Csn-B), a NR4A1-specific agonist, significantly reduces severity of disease. Effects of Csn-B were absent in monocyte-depleted mice treated with clodronate until Ly6C monocytes were restored. Adoptive transfer of Ly6C monocytes in arthritic NR4A1 mice treated with Csn-B reduces joint inflammation, supporting the regulatory role of Ly6C subset on disease development. Our results also reveal that administration of Csn-B to arthritic mice enhances levels of circulating CD4 CD25 FoxP3 Treg cells, a process requiring the presence of Ly6C monocytes. Together, these data indicate that Ly6C monocytes are involved in the initiation and progression of arthritis and Ly6C monocytes contribute to reduce joint inflammation through the mobilization of Treg cells.
单核细胞是关节炎病理生理学的核心，但它们在疾病的进展和缓解中的作用仍需阐明。使用缺乏巡逻淋巴细胞抗原 6C（Ly6C）单核细胞的 NR4A1 小鼠，我们发现炎症性 Ly6C 单核细胞有助于血清转移诱导关节炎（STIA）模型中关节炎的快速发展。我们的实验表明，巡逻单核细胞不会促进小鼠关节炎的起始和进展，因为症状的严重程度在 NR4A1 小鼠中放大。此外，我们表明，用 NR4A1 特异性激动剂胞嘧啶 B（Csn-B）治疗关节炎野生型（WT）小鼠可显著减轻疾病严重程度。在用 clodronate 处理的单核细胞耗竭小鼠中，Csn-B 的作用消失，直到恢复 Ly6C 单核细胞。在接受 Csn-B 治疗的关节炎 NR4A1 小鼠中过继转移 Ly6C 单核细胞可减轻关节炎症，支持 Ly6C 亚群对疾病发展的调节作用。我们的结果还表明，向关节炎小鼠给予 Csn-B 可提高循环 CD4 CD25 FoxP3 Treg 细胞的水平，这一过程需要 Ly6C 单核细胞的存在。总之，这些数据表明 Ly6C 单核细胞参与关节炎的起始和进展，Ly6C 单核细胞通过动员 Treg 细胞有助于减轻关节炎症。
