TGF-β+CD11c+DC逆转活化型Treg缺陷对变应性鼻炎Th1/Th2免疫失衡的调控

Allergic rhinitis (AR) is nasal mucosa of chronic inflammation caused by the immune imbalance of Th1/Th2. We previously reported that the active Treg(aTreg) insufficiency of AR patients played a critical role in the Th1/Th2 immune imbalance of upper allergic airway inflammation. Therefore, reversing the Treg insufficiency is expected to be an important means of the immunotherapy for AR. Our previous experiments found that the tolerogenic DC (TolDC) were lower in AR than normal groups and correlated with the decrease of aTreg. Additionally, TolDC highly secreted IL-10 and TGF-β, which played a vital role in the differentiation and development of Treg. We hypothesize that inducing the differentiation and development of TolDC could reverse the aTreg insufficiency, thus recovering the immune imbalance of Th1/Th2. In this project, we will apply the co-cell culture system to investigate the immunomodulation and interaction mechanisms between TolDC and aTreg, and establish a mouse model of AR and asthma to investigate the immunomodulation in upper airway allergic inflammation via adoptive transferring TolDC. This project will help clarify the immunomodulation mechanisms of TolDC via inducing aTreg, and thus providing a new strategy for treating allergic rhinitis.

变应性鼻炎（AR）是由Th1/Th2免疫失衡引起的鼻粘膜慢性炎症。我们前期报道AR患者活化型调节性T细胞（aTreg）缺陷是导致上气道变应性炎症Th1/Th2免疫失衡的关键要素。因此，通过扭转AR患者aTreg缺陷有望成为AR免疫治疗的重要手段。我们预实验发现：与健康人群相比，AR患者免疫耐受型树突状细胞（TolDC）比例降低，且与aTreg下降呈正相关；此外，TolDC高分泌IL-10和TGF-β。鉴于上述两种细胞因子在Treg分化发育中扮演的重要角色，我们提出假设：通过诱导AR患者TolDC的产生可扭转aTreg缺陷，进而逆转AR患者Th1/Th2免疫失衡。本课题拟应用体外实验明确TolDC对aTreg的免疫调控及相互作用机制；体内实验探讨过继输注TolDC能否改善AR小鼠上气道变应炎症。本研究将有助于阐明AR中TolDC诱导aTreg发挥免疫调控功能的具体机制，为AR的防治提供新思路

变应性鼻炎（AR）是由Th1/Th2免疫失衡引起的鼻粘膜慢性炎症。本课题研究发现在体外实验中，经Derp-1变应原刺激的单核细胞来源的Tol DCs可通过转化生长因子β/白细胞介素-10 (TGF-β/IL-10)依赖的方式促进活化Tregs (aTregs)的产生，并抑制Th2型细胞反应。BM-Tol DC的过继转移可通过TGF-β/IL-10信号通路促进aTreg的分化增殖，抑制OVA致敏AR小鼠模型的过敏性气道炎症反应。综上通过针对tDCs的分化和/或扩增策略重建AR免疫和耐受性之间的平衡，为AR的防治提供新思路。