iPSC-MSCs通过树突状细胞调控鼻息肉Th2型炎症及机制探讨

我们报道了多能干细胞来源的间充质干细胞（iPSC-MSC）可抑制气道变应性炎症，且其可调控树突状细胞（DC）的分化及功能。最新研究发现嗜酸粒细胞性鼻息肉（Eos-NP）亦属类似于变应性炎症的Th2型炎症，且DC在其发病中具有重要作用，但iPSC-MSC对鼻息肉的作用未见报道。我们前期证实iPSC-MSC可下调Eos-NP中的Th2型细胞因子，由此我们假设iPSC-MSC可通过DC调控鼻息肉Th2型炎症。本研究拟应用体外共培养，分离Eos-NP细胞而验证iPSC-MSC对Eos-NP中Th2型炎症的调节作用；分离Eos-NP中的DC而确定iPSC-MSC可通过DC抑制Eos-NP的Th2型炎症；进一步应用Transwell、中和性抗体/阻断剂等揭示其中的分子机制，这将为目前Eos-NP 的防治提供以干细胞为基础的全新方案，也为以DC为新靶点的治疗方案提供有力的理论依据，具有深远的应用前景。

We have reported induced pluripotent stem cell-derived mesenchymal stem cell (iPSC-MSC) was able to suppress allergic airway inflammation and modulate the differentiation and function of dendritic cell (DC). Recent studies demonstrated that eosinophilic nasal polyps (Eos-NP) is characterised by T-helper type 2 inflammation which is similar to allergic inflammation, and DC plays an important role in the pathogenesis of Eos-NP. However, the effect of iPSC-MSC on nasal polyps remains unknown. Our preliminary findings showed iPSC-MSC is able to decrease T-helper type 2 cytokines. Thus, we hypothesize iPSC-MSC could modulate T-helper type 2 inflammation in nasal polyps via dendritic cells. In the present study, we plan to separate Eos-NP cells to co-culture with iPSC-MSC, analyze the immunomodulatory effect of iPSC-MSC on the T-helper type 2 inflammation in Eos-NP; to purify DC from Eos-NP to co-culture with iPSC-MSC, examine the role of DC in the immunomodulatory effect of iPSC-MSC on T-helper type 2 inflammation in Eos-NP; to employ Transwell system, neutralizing antibody or antagonist to further investigate the molecular mechanisms of the immunomodulatory effect of iPSC-MSC. This study will provide a bran-new stem cell-based therapy for the treatment of Eos-NP and provide good theoretical foundation for the new treatment strategy targeting DC.