过表达IL-17RLM羊水间充质干细胞靶向调控IL-23/Th17轴对克罗恩病的治疗作用及机制

克罗恩病（Crohn's disease, CD）是机体免疫紊乱导致的肠道炎性疾病，发病机制未明，传统疗法效果欠佳，预后差。两种新的疗法效果显著但有诸多不足，如干细胞治疗取材难、免疫调节特异性差；靶向治疗不能持续起效，难以维持。人羊水间充质干细胞（amniotic fluid-derived mesenchymal stem cells, AF-MSCs）同时具有胚胎来源及成体来源干细胞特性，是优秀的种子细胞。新近研究发现IL-23/Th17轴是CD免疫紊乱的关键信号通路，IL-17是IL-23/Th17轴的效应分子，是靶向治疗的合适靶点。我们拟采用慢病毒载体将IL-17受体融合蛋白（IL-17RLM）基因转入hAF-MSCs，建立稳定的过表达IL-17RLM 的AF-MSCs细胞系，调控IL-17表达，互补靶向与干细胞治疗优势，研究其对IL-23/Th17信号轴的调控及对CD的治疗机制。

Crohn's disease (CD) is one of the inflammatory bowel disease with unknown pathogenesis but definitive relationship with autoimmune disorders.The effects of conventional treatments are limited and hard to maintain. The newly two promising therapies both have their own disadvantages,such as poor immunoregulation specificity for stem cell therapy and non-sustainable effect for targeted therapy. Amniotic fluid-derived mesenchymal stem cells(AF-MSCs) have been proved to be with both the characteristics of embryonic stem cell and adult stem cell in our previous study and could be well-chosen as ideal seeding cells for stem cell therapy for CD.Recent studies identified that IL-23/Th17 axis was the key signaling pathway of CD immune disorders.IL-17,the effector molecule of IL-23/Th17 axis，has been defined as a suitable target of immuno-targeted therapy for CD. We intend to establish a stably over expressing IL-17RLM stem cell line via interleukin-17 receptor like molecule(IL-17RLM）modified AF-MSCs by means of lentivirus vector, effectively and sustainedly down-regulate IL-17. We expect to complement these two new remedies by recombinant stem cells and provide a new prospective way to treat CD.