中国人兽共患病学报2024,Vol.40Issue(6) :529-536.DOI:10.3969/j.issn.1002-2694.2024.00.091

LAG3分子对泡球蚴感染小鼠肝脏B淋巴细胞亚群及其功能的影响

Effect of LAG3 molecule on B lymphocyte subsets and its function in the liver of mice infected with Echinococcus multilocularis

郑旭然 邓冰清 康雪娇 李寅时 阿比旦·艾尼瓦尔 余倩 孜比姑·肉素 阿迪莱·多力坤 王茂林 王慧 张传山 李静
中国人兽共患病学报2024,Vol.40Issue(6) :529-536.DOI:10.3969/j.issn.1002-2694.2024.00.091

LAG3分子对泡球蚴感染小鼠肝脏B淋巴细胞亚群及其功能的影响

Effect of LAG3 molecule on B lymphocyte subsets and its function in the liver of mice infected with Echinococcus multilocularis

郑旭然 1邓冰清 1康雪娇 1李寅时 1阿比旦·艾尼瓦尔 1余倩 1孜比姑·肉素 1阿迪莱·多力坤 1王茂林 1王慧 1张传山 1李静2
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作者信息

  • 1. 新疆医科大学基础医学院,乌鲁木齐 830054;新疆医科大学第一附属医院临床医学研究院、省部共建中亚高发病成因与防治国家重点实验室、新疆维吾尔自治区包虫病基础医学重点实验室,乌鲁木齐 830054
  • 2. 新疆医科大学基础医学院,乌鲁木齐 830054;新疆地区高发疾病研究教育部重点实验室(新疆医科大学),乌鲁木齐 830054;新疆维吾尔自治区地方病分子生物学重点实验室,乌鲁木齐 830054
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摘要

目的 探究淋巴细胞活化基因-3(Lymphocyte activation gene-3,LAG3)分子对泡球蚴感染小鼠肝脏B淋巴细胞亚群及其功能的影响.方法 将野生型(C57-wild-type,WT)和LAG3基因敲除(LAG3-knockout,LAG3-KO)小鼠经肝门静脉注射泡球蚴原头节,感染12周免疫组织化学染色观察小鼠肝脏CD19和α-SMA表达及定位,流式细胞术检测小鼠肝脏B细胞及其各亚群和表面CD80、CD86、MHC-Ⅱ分子的表达情况.结果 泡球蚴感染12周小鼠肝脏LAG3-KO组CD19阳性区及面积占比略高于WT组,但差异均无统计学意义.α-SMA在LAG3-KO组阳性区及面积占比显著高于WT组(t=-3.224、-3.227,P均<0.05).LAG3-KO组肝脏B细胞表达CD80和MHC-Ⅱ分子的比例显著上调,差异具有统计学意义(t=-2.379、-3.321,P均<0.05).LAG3-KO组B2细胞占比显著高于WT组,差异有统计学意义(t=-2.695,P<0.05).LAG3-KO组Bib细胞表达CD80比例亦显著上调,差异具有统计学意义(t=-5.315,P<0.001),而B2细胞表达CD80比例显著低于WT组,且差异具统计学意义(t=2.806,P<0.05).LAG3-KO组B2细胞表达MHC-Ⅱ分子显著上调,且具统计学差异(t=-4.227,P<0.01).结论 泡球蚴感染中期12周,LAG3分子影响小鼠肝脏B细胞亚群及功能,并以B2型淋巴细胞尤为显著,LAG3对B细胞的活化以及MHC-Ⅱ类分子表达产生抑制作用,提示其可能参与泡球蚴感染下的B细胞耗竭.

Abstract

This study was aimed at investigating the effect of lymphocyte activation gene-3(LAG3)on liver B lymphocyte subsets and their functions in WT and LAG3-KO mice infected with Echinococcus multilocularis(E.multilocularis).In a mouse model of E.multilocularis infection,the expression and localization of CD19 and α-SMA in liver were detected by immu nohistochemistry.CD80,CD86 and MHC-Ⅱ molecules expressed on B cells and their subsets in mice liver were detected by flow cytometry.After 12 weeks of infection,the area and percentage of CD19 in LAG3-KO group was slightly higher than that in WT group,but the difference was not statistically(t=-1.241、-1.237,P>0.05).The area and percentage of a-SMA in LAG3-KO group was higher than that in WT group(t=-3.224、-3.227,P<0.05).The proportion of CD80 and MHC-Ⅱ molecules expressed on liver B cells in LAG3-KO group was up-regulated(t=-2.379,-3.321,P<0.05).The percentage of liver B2 cells in LAG3-KO group was higher than that in WT group(t=-2.695,P<0.05).The expression of CD80 on Blb cells in LAG3-KO group was significantly up-regulated(t=-5.315,P<0.001).The proportion of CD80 of B2 cells in LAG3-KO group was lower than that in WT group(t=2.806,P<0.05).The expression of MHC-Ⅱ molecule in B2 cells in LAG3-KO group was up-regulated(t=-4.227,P<0.01).It is suggested that LAG3 molecules affected the B cell subsets and func-tion of mouse liver in the middle stage of E.multilocularis infection,especially B2 lymphocytes.LAG3 molecule exerted an in-hibitory effect on the activation of B cells and the expression of MHC-class Ⅱ molecules,suggesting that it may be involved in B cell exhaustion caused by E.multilocularis.

关键词

泡球蚴/淋巴细胞活化基因-3/B细胞/B细胞亚群

Key words

Echinococcus multilocularis/LAG3/B cells/B cell subsets

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基金项目

国家自然科学基金(82060370)

国家自然科学基金(82302561)

国家自然科学基金(82372279)

新疆维吾尔自治区自然科学基金(2022D01E51)

新疆维吾尔自治区自然科学基金(2022D01D60)

新疆地区高发疾病研究教育部重点实验室开放课题资助项目(2023B03)

出版年

2024
中国人兽共患病学报
中国微生物学会

中国人兽共患病学报

CSTPCD北大核心
影响因子:0.814
ISSN:1002-2694
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