新细胞因子CSBF在干眼中发挥免疫保护作用的机制研究

目前研究表明Th17细胞及其相关细胞因子在干眼中发挥重要致病作用。然而部分对Th17细胞具有负向调控作用的细胞因子尚未得到阐明。我们的前期研究表明，一种新细胞因子CSBF（结肠衍生的SUSD2结合蛋白）在干眼小鼠角膜中表达水平升高；Csbf敲除小鼠干眼表型加重，且引流淋巴结中Th17细胞比例增加。因此我们推测，CSBF可以抑制Th17细胞的分化、增殖、活化及迁移，促进其凋亡，从而在干眼中起到免疫保护作用。因此，在前期实验基础上，本项目将通过体内外实验研究干眼条件下CSBF对Th17细胞的抑制作用，并深入探讨其作用的受体和信号通路。同时，我们将建立人体泪液中CSBF蛋白水平的检测方法，并通过临床研究分析其与干眼诊断指标的相关性。本项目试图通过上述研究，阐明新细胞因子CSBF在干眼中发挥免疫保护作用的机制，完善干眼免疫中Th17细胞的调控环路，为干眼的生物学诊断及免疫治疗提供重要依据。

It has been proved that Th17 cells and associating cytokines play vitally pathogenic roles in dry eye disease(DED). However, some cytokines that may inhibit the functions of Th17 cells remain unexploited. Our previous data showed that a novel cytokine named CSBF(Colon-derived SUSD2 binding factor) was upregulated in cornea of dry eye mouse model. Worse injury and more inflammation were found in cornea of the Csbf knock out mouse under dry eye condition, and more Th17 cells were observed in the draining lymph nodes. Therefore, it is reasonable to hypothesize that CSBF plays an important role in alleviating dry eye immune response by inhibiting the differentiation, proliferation, activation and migration of Th17 cells and promoting the apoptosis. Based on our previous work，we will investigate the inhibitory functions of CSBF on Th17 cells in dry eye mouse model and in vitro, and figure out the receptor and signaling pathway in the process. Meanwhile, we will set up the method to detect the level of CSBF in tears of people, and analyze the correlation of CSBF expression and diagnostic markers of DED by clinical research. This study will uncover the mechanism of a novel cytokine CSBF and its immune-protective effects in DED, investigate the regulating system of Th17 cells related immune response in DED, and provide an important clue for biological diagnosis and immunological therapy for DED.