真菌菌群紊乱对肠道固有淋巴细胞的调节在DSS肠炎小鼠肠黏膜免疫中的作用研究

Dysfunction of mucosal immunity and dysbiosis of microbiota in gut are two main features of inflammatory bowel diseases（IBD）, which interact with each other. Increasing reports highlighted the pivotal role of innate lymphoid cells (ILCs) in chronic inflammation. Although fungal dysbiosis in IBD patients and animals was proved indeed, it remains unknown if fungal dysbiosis participates in pathogenesis and development of IBD via regulating ILCs function. In our previous study, treated with high dose of fluconazole, significant changes in fungal microflora and aggravated symptoms of inflammation could be found in mice with dextran sodium sulphate (DSS)-induced colitis. With learning related reports, we inferred that this phenomenon was related with ILCs. Based on this hypothesis, we will use two methods (fluconazole treatment and Candida albicans infection) to model the fungal dysbiosis in wild and Rag 1/2 knockout mice, and then to elucidate the regulation effect of fungal dysbiosis on composition and functions of ILCs, and to primarily explore its mechanism. Additionally, to clarify the process that ILCs regulated by fungal dysbiosis can aggravate DSS-induced colitis, 1) we will make DSS-induced colitis in wild mice to detect ILCs changes in the condition of coexisting of fungal dysbiosis and DSS-induced colitis, and 2) reinfusion of ILCs (from mice with fungal dysbiosis) to normal wild mice will be performed, and followed by DSS treatment. Altogether, we could further illustrate the regulatory effect of microbial dysbiosis on mucosal immunity in IBD by performing this study.

炎症性肠病(IBD)的特点是肠黏膜免疫失衡、肠道微生态紊乱,两者相互作用。固有免疫细胞(ILCs)在慢性炎症中具有重要作用,尽管IBD患者和小鼠中均见真菌菌群紊乱,但其是否调节ILCs功能并参与IBD的发生发展尚未可知。在我们前期研究中,大剂量氟康唑处理后，硫酸葡聚糖钠(DSS)肠炎小鼠肠道真菌菌群菌群明显紊乱，炎症显著加重,我们推测这与ILCs功能变化有关。本研究将通过两种方法(氟康唑处理和白色念珠菌感染)在野生型和Rag1/2敲除小鼠中制备真菌紊乱模型，探讨其对ILCs的调节作用，并初步探索其机制。我们还将制备DSS肠炎模型，观察真菌菌群紊乱和DSS对小鼠肠道同时作用时，ILCs的变化特点。此外，我们还将回输ILCs细胞给正常小鼠，随后诱导DSS肠炎，进一步阐明真菌菌群紊乱可通过调节ILCs功能参与小鼠DSS肠炎的发展与加重。该研究将进一步诠释IBD中微生态紊乱对肠粘膜免疫的调节作用。

炎症性肠病(IBD)的特点是肠黏膜免疫失衡、肠道微生态紊乱,两者相互作用。固有免疫细胞(ILCs)在慢性炎症中具有重要作用,尽管IBD患者和小鼠中均见真菌菌群紊乱,但其是否调节ILCs功能并参与IBD的发生发展尚未可知。在我们前期研究中,大剂量氟康唑处理后，硫酸葡聚糖钠(DSS)肠炎小鼠肠道真菌菌群菌群明显紊乱，炎症显著加重,我们推测这与ILCs功能变化有关。本研究将通过两种方法(氟康唑处理和白色念珠菌感染)在野生型和Rag1/2敲除小鼠中制备真菌紊乱模型，探讨其对ILCs的调节作用，并初步探索其机制。我们还将制备DSS肠炎模型，观察真菌菌群紊乱和DSS对小鼠肠道同时作用时，ILCs的变化特点。此外，我们还将回输ILCs细胞给正常小鼠，随后诱导DSS肠炎，进一步阐明真菌菌群紊乱可通过调节ILCs功能参与小鼠DSS肠炎的发展与加重。该研究将进一步诠释IBD中微生态紊乱对肠粘膜免疫的调节作用。