敲除CD226通过调节小鼠脾脏和肠道免疫细胞比例缓解小鼠的慢性束缚应激引起的抑郁样行为  

Knockout of CD226 alleviates depression-like behavior induced by chronic restraint stress in mice by modulating the ratio of immune cells in spleen and intestine

作　　者：王婷婷 羊璐 马菁昌 王玉玲 程坤 庄然 吕玉红 WANG Tingting;YANG Lu;MA Jingchang;WANG Yuling;CHENG Kun;ZHUANG Ran;LYU Yuhong(Yan'an Key Laboratory of Microbial Drug Innovation,Medical School of Yan'an University,Yan'an 716000;Department of Immunology of the Air Force Medical University,Xi'an 710032,China)

机构地区：[1]延安大学医学院微生物药物创新与转化重点实验室,陕西延安716000 [2]空军军医大学基础医学院免疫学教研室,陕西西安710032

出　　处：《细胞与分子免疫学杂志》2023年第3期242-248,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81871258,82060654);空军军医大学“珠峰计划”(2020rcfczr)。

摘　　要：目的探讨CD226在小鼠慢性束缚应激(CRS)诱导的抑郁样行为中发挥的免疫调控作用及其可能机制。方法选取4~6周龄野生型(WT)雄性C57/BL6J和同品系CD226基因敲除(CD226KO)小鼠建立CRS模型,通过强迫游泳测试、蔗糖偏好测试等行为学检测方法对小鼠进行应激抑郁评分,利用流式细胞术分析脾脏、Peyer淋巴结及肠上皮内淋巴细胞亚群的差异。结果与WT CRS组相比,CD226KO CRS组强迫游泳测试静止时间显著降低,蔗糖偏好率显著上升;脾脏CD4+T细胞和CD8+T细胞之比显著降低;小肠上皮内淋巴细胞中T细胞受体αβ(TCRαβ)和TCRαβCD8αβ细胞亚群比例显著升高。结论敲除CD226能够缓解小鼠CRS模型诱导的抑郁样行为,影响CRS状态下小鼠脾脏及肠道免疫细胞比例,改善小鼠应激状态下的整体免疫状态。Objective To investigate the immunoregulatory effects of CD226 on the chronic restraint stress(CRS)-induced depression-like behavior and its underlying mechanism in mice.Methods Male C57/BL6J mice and CD226 gene knockout(KO)mice with the same strain(4-6 week old)were adopted to establish CRS models.The stress-induced depression scores of mice were evaluated through behavioral testing such as forced swimming test and sucrose preference test.Flow cytometry was used to analyze the differences of the intraepithelial lymphocytes in the spleens,peyer's patches,and intestines between the two groups.Results Compared with WT CRS group,mice in CD226KO CRS group showed significantly decreased immobility time in forced swimming test and increased sucrose preference rate.The ratio of CD4+T cells to CD8+T cells in spleen was significantly reduced,combined with the remarkably elevated proportion of TCRaβand TCRaβCD8αβcells in the small intestinal IELs of CD226 KO mice with CRS.Conclusion Knockout of CD226 alleviates CRS-induced depression-like behavior in mice,alters the proportion of immune cells in murine spleen and intestine,and improves the overall immune status of mice under stress.

关 键 词：慢性束缚应激(CRS) CD226 肠上皮内淋巴细胞 

分 类 号：R749.41[医药卫生—神经病学与精神病学] R392.12[医药卫生—临床医学] R331.144