Transcriptomic Analysis of Isolated Monocytes from heathy donors and JIA patinets using Nanostring Technology. Transcriptomic Analysis of Isolated Monocytes from heathy donors and JIA patinets using Nanostring Technology

Among immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies. The uncontrolled activation of monocytes and the subsequent excessive production of inflammatory factors damage bone-cartilage joints in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. The moderate beneficial effect of current therapies and clinical trials highlights the need of alternative strategies targeting monocytes to treat RA disease. Here, we show that targeting CXCR4 with small amino compound such as the histamine analog clobenpropit (CB) inhibits spontaneous and induced-production of a set of key inflammatory cytokines by monocytes isolated from blood and synovial fluids of JIA patients. Moreover, daily intraperitoneal CB treatment of arthritic mice results in significant decrease in circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption leading to reduction of disease progression. These overall data show that targeting CXCR4 with CB-like molecules may represent a promising therapeutic option for chronic and viral-induced inflammatory diseases. Overall design: Total of 6 Samples: Three from Healthy Donors and Three from OligoAJI Patients

在免疫细胞群体中，活化单核细胞在慢性炎症及病毒诱导性炎症病变中发挥有害作用。单核细胞的失控活化与后续炎症因子的过量产生，会损伤幼年特发性关节炎（Juvenile Idiopathic Arthritis, JIA）——一类儿童类风湿关节炎（Rheumatoid Arthritis, RA）——患者的骨软骨关节。现有疗法与临床试验仅能带来适度获益，这凸显出开发靶向单核细胞的替代治疗策略以干预RA的必要性。
本研究证实，使用组胺类似物氯苯丙替（clobenpropit, CB）这类小分子氨基化合物靶向CXCR4，可抑制从JIA患者血液及滑液中分离的单核细胞自发产生与诱导产生的一系列关键炎症细胞因子。此外，对关节炎模型小鼠每日开展腹腔注射CB治疗，可显著降低循环炎症细胞因子水平、免疫细胞浸润程度、关节侵蚀及骨吸收情况，从而延缓疾病进程。
综上，采用CB类分子靶向CXCR4，或可成为慢性炎症及病毒诱导性炎症疾病的极具潜力的治疗选择。
实验设计：共计6份样本，其中3份来自健康供体，3份来自少关节型JIA（OligoAJI）患者。