CD200R在炎症性肠病中的作用及机制研究

炎症性肠病（IBD）确切的病因和发生机制不清楚，可能与肠道黏膜免疫异常相关。CD200-CD200R通路在细胞免疫调节中发挥重要作用。我们前期研究发现，IBD患者外周血及肠道黏膜中性粒细胞CD200R下调；初步的动物实验显示小鼠CD200R靶向缺陷中性粒细胞免疫学功能异常，并导致结肠炎小鼠肠黏膜损伤加重及修复延缓，表明中性粒细胞CD200R缺陷与IBD发生发展相关，提示上调CD200R表达将可能恢复中性粒细胞免疫学功能，并可能在防治IBD中发挥重要作用。本项目以纳米微粒BSA-Chit-CD200R靶向上调小鼠CD200R-/-中性粒细胞CD200R表达，研究靶向上调CD200R表达对中性粒细胞代谢及免疫功能的调节作用，或以正常表达CD200R小鼠中性粒细胞回输中性粒细胞CD200R-/-小鼠，分析这些调节对小鼠结肠炎的保护作用及其机制，探讨CD200R能否成为IBD临床精准诊疗的新靶点。

Inflammatory bowel disease (IBD) is chronic, relapsing and remitting inflammatory disease of the gastrointestinal tract. Abnormal immune responses in intestinal mucosa toward commensal bacterial flora may be associated with the etiology and pathogenesis of human IBD. The CD200R is a critical negative regulator of innate immune responses. Our recent studies showed CD200R expression is reduced on neutrophils from peripheral blood and intestinal mucosa from patients with IBD；CD200R deficiency drives inflamed yet incompetent neutrophils and fails to produce mediators related to mucosal repair in DSS induced colitis in mice, which leads to more serious mucosal injure and delays mucosal repair. These results indicate that deficiency of CD200R contributes to the progress of colitis through disturbing neutrophil immunological functions. However, the behind mechanism still remains elusive. Our proposal will explore the role of CD200R on mucosal repair and barrier re-building through regulating immunity and metabolic of neutrophil with CD200R targeting deficiency by up-regulating CD200R expression targeting neutrophil with nanoparticle of BSA-Chit-CD200R and further explore whether CD200R could be a new target for accurate diagnosis and treatment and prognosis evaluation of IBD.