炎症性肠病（IBD）的发生与肠黏膜免疫对肠道微生物产生过激的免疫应答等因素相关，Tollip是TLRs介导的肠黏膜免疫反应中重要的负性调控因子。我们前期研究发现，活动期IBD患者外周血中性粒细胞及病变部位肠黏膜Tollip表达降低；DSS诱导的Tollip基因敲除小鼠结肠炎模型中，中性粒细胞免疫活性下降，肠黏膜损伤加重及修复延缓。表明中性粒细胞Tollip表达下调与IBD发病相关，提示上调Tollip表达可能恢复中性粒细胞免疫学功能，并可能在预防和治疗IBD中发挥重要作用。本项目将在前期研究基础上，以基于纳米技术构建的纳米微粒BSA-Chit-Tollip在小鼠体内靶向上调中性粒细胞Tollip表达，研究上调Tollip表达对中性粒细胞免疫学功能的调节作用机制以及进一步对DSS诱导的小鼠结肠炎发挥预防和治疗作用机制，为探讨Tollip能否成为IBD临床精准诊断和治疗的新靶点提供坚实的依据。

Abnormal immune responses in intestinal mucosa toward commensal bacterial flora may be associated with the etiology and pathogenesis of human IBD. The Toll-interacting protein (Tollip) is a critical negative regulator of Toll-like receptor (TLR)-mediated innate immune responses. Our recent studies showed Tollip expression is reduced on neutrophils and intestinal mucosa from patients with active IBD; Tollip 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 Tollip contributes to the progress of colitis,suggesting that up-regulation of Tollip may restore neutrophil immunological function and play an important role in the prevention and treatment of IBD. In this study, we will further investigate the immunological functions of neutrophil in DSS induced colitis in mice by targeting up-regulation of Tollip with nanoparticle BSA-Chit-Tollip. This work will determine the potential role of Tollip in the pothogenesis of IBD and explore whether Tollip could be a new target for accurate diagnosis and treatment and prognosis evaluation of IBD.