多形拟杆菌通过ICOS+Tregs对小鼠呼吸道变应性炎症的免疫调控和机制研究

Recent studies have reported that gut microbiota could inhibit respiratory allergic inflammation, and induce costimulatory molecules (ICOS) + regulatory T cells (Tregs) may play an important role. Our study demonstrated that in application of the microbial macro genome 16SrDNA analysis, the abundance of bacteroides in the fecal intestinal flora of allergic rhinitis patients and mice significantly decreased, compared with that in the normal population and mice. And our study also confirmed that ICOS gene expression in patients with allergic rhinitis increased via gene expression profiling chip. Bacteroides thetaiotaomicron is one of the largest number of anaerobic bacteria in the gut microbiota. It has function of actively regulating the human gene and decomposing cellulose which human itself could not decompose. Therefore, we hypothesize that bacteroides thetaiotaomicron could regulate respiratory allergic inflammation via ICOS+Tregs. In the present study, we have successfully cultivated bacteroides thetaiotaomicron by strict anaerobic culture technique, and have confirmed that it could be stably colonized in the intestine of mice. Following, we plan to evaluate the immunomodulation of bacteroides thetaiotaomicron on allergic airway inflammation in mice, and to further examine the role of ICOS+Tregs with the application of flow and blocking antibodies to reveal the molecular mechanism. This study will provide a bran-new gut microbiota -based therapy for the treatment of allergic rhinitis, and will provide a good new treatment strategy targeting ICOS+Tregs.

最新研究报道了肠道菌群可抑制呼吸道变应性炎症，且可诱导共刺激分子(ICOS)+的调节性T细胞(Tregs)在其中发挥重要作用。我们采用微生物宏基因组16SrDNA技术分析发现：同正常人群和小鼠相比，变应性鼻炎患者和小鼠粪便的肠道菌群中拟杆菌门的丰度明显下降；且基因表达谱芯片扫描证实ICOS基因在变应性鼻炎患者体内表达上升。多形拟杆菌是肠道厌氧菌中数量最大菌群之一，具有主动调节人体基因和分解人体自身无法分解的纤维素等功能，由此我们假设多形拟杆菌能通过ICOS+Tregs“遥控”呼吸道变应性炎症。本研究采用严格的厌氧菌培养技术培养了多形拟杆菌，并证实其在小鼠肠道内可稳定定植；拟应用多形拟杆菌对小鼠的呼吸道变应性炎症进行免疫干预，并进一步应用流式和阻断性抗体等揭示其中的分子机制。这将为变应性鼻炎的防治提供以肠道菌群为中心的新的思路，并为以ICOS+Tregs为靶点的治疗提供理论依据，前景深远。

相关研究报道了肠道菌群可抑制呼吸道变应性炎症，且可诱导共刺激分子(ICOS)+的调节性T细胞(Tregs)在其中发挥重要作用。多形拟杆菌是肠道厌氧菌中数量最大菌群之一，具有主动调节人体基因和分解人体自身无法分解的纤维素等功能。本研究发现了:①同正常人群和小鼠相比，变应性鼻炎患者和小鼠粪便的肠道菌群中拟杆菌门的丰度明显下降；且基因表达谱芯片扫描证实ICOS基因在变应性鼻炎患者体内表达上升；②采用严格的厌氧菌培养技术培养了多形拟杆菌，证实了其在小鼠肠道内可稳定定植；③应用多形拟杆菌对小鼠的呼吸道变应性炎症进行干预，揭示了ICOS+Tregs激活并抑制TH2反应的免疫机制。这将为变应性鼻炎的防治提供以肠道菌群为中心的新的思路，并为以ICOS+Tregs为靶点的治疗提供可靠依据。