CD226调控单核细胞迁移和巨噬细胞活化在溃疡性结肠炎发生发展中的作用和分子机制

溃疡性结肠炎（ulcerative colitis，UC）是一种严重危害人体健康的炎症性疾病，血液中不同亚群单核细胞趋化迁移至肠黏膜固有层并转化为功能不同的巨噬细胞在UC发生、发展中发挥重要调节作用，但不同亚群单核细胞肠道组织迁移和巨噬细胞活化在UC中的作用及其调节机制仍不清楚。CD226分子高水平表达于炎性单核细胞表面，我们发现UC模型小鼠肠组织中CD226+F4/80+巨噬细胞增多；Cd226-/-小鼠UC病情减轻；体外刺激促进Cd226-/-巨噬细胞向M2型极化。提示：CD226可能通过调控单核细胞迁移和巨噬细胞活化参与UC的发生和发展。本课题以小鼠和人的巨噬细胞为研究对象，明确CD226在UC单核细胞肠道组织迁移中的作用和机制，阐明其调节巨噬细胞活化的机制，搞清CD226通过调控单核细胞迁移和巨噬细胞活化在UC发病中的作用，为探索UC的发生发展机制和临床治疗策略提供新的靶点和思路。

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease that does a serious hazard to human health. Migration of different monocyte subpopulations from the blood vessels into the intestinal lamina propria and porlarization of macrophages into different subpopulations with different functions play important regulatory roles in the occurrence and development of UC. However, the role and regulatory mechanisms of monocyte subset migration from the blood vessels into intestinal tissues and macrophage porlarization in the occurrence and development of UC remain unclear. CD226 molecule is highly expressed on the surface of inflammatory monocytes. Our early study found that the number of CD226+F4/80+ macrophages increased in the intestinal tissues in the UC mouse model, Cd226-/-mouse alleviated UC progression, and CD226 knockout in macrophages significantly enhanced the alternative activation (M2) of macrophages. The above results indicate that CD226 may participate in the occurrence and development of UC by regulating monocyte migration and macrophage activation. In the current project, mouse and human monocytes and macrophages were used to explore the role of CD226 in the migration of monocytes from blood vessels into intestinal tissues, to clarify the mechanisms of CD226 regulating macrophage activation, and to verify the role and mechanisms of CD226 regulating monocyte migration and macrophage activation in UC occurrence and development. These studies are expected to provide new targets and ideas for exploring the progression mechanisms and the treatment strategies to improve UC treatment.