溃疡性结肠炎（UC）是一种病因不明,治愈率低，易复发的炎症性肠道疾病。肠道巨噬细胞功能失调在UC发生、发展中发挥重要作用。我们的研究发现COP9信号复合体 CSN8亚基在调控溃疡性结肠炎肠黏膜巨噬细胞介导的炎症反应中起关键作用。UC模型中,巨噬细胞CSN8条件性敲基因小鼠的疾病症状明显减轻，生存期明显延长。体外实验表明，TLR4和TLR2配体（LPS和Pam3CSK4）刺激CSN8条件性敲基因小鼠骨髓细胞体外诱导的巨噬细胞，其炎症细胞因子TNF-α产生的量以及共刺激分子CD80，4-1BBL的表达明显下降，而负性共刺激分子B7-H1表达显著上升。本研究在原有实验基础上，从分子、细胞、条件性敲基因小鼠动物模型、组织病理和临床随访等不同层面，探讨CSN8在溃疡性肠病肠道巨噬细胞生物学行为调控中的作用及机制，为探索溃疡性结肠炎的发病机理和治疗靶点提供新的理论基础和实验依据。

Ulcerative colitis is a intractable and relapsing inflammatory bowel disease of unknown causation. Dysfunction of macrophage plays important roles in occurrence and development of ulcerative colitis. We found that CSN8 served as crucial roles in regulating inflammatory responses mediated by macrophages in colonic mucosa of ulcerative colitis.In DSS induced colitis model, CSN8-deficient mice displayed that their colon mucosal injury was alleviated and survival time was prolonged, and their bone marrow cell drived macrophages stimulated by LPS or Pam3CSK4 pruduced lower level of TNF-α, expressed lower level of CD80 and 4-1BBL and higher level of B7-H1. Based on the previous findings, in this study, we further investigate the biological function of colonic mucosa macrophage of ulcerative colitis and the mechanism regulated by CSN8 through defferent levels, such as molecule,cell, animal model, pathological tissue,clinical follow-up investigation. Our studies may provide new theoretical and experimental basis for exploring pathogenesis and therapeutic targets of ulcerative colitis.