[1]宋亚茹,田雪钦,赵雨欣,等.肿瘤坏死因子α诱导蛋白8样分子2在T细胞发育过程中的表达及其对哮喘发病的潜在作用[J].新乡医学院学报,2022,39(12):1101-1106.[doi:10.7683/xxyxyxb.2022.12.001]
　SONG Yaru,TIAN Xueqin,ZHAO Yuxin,et al.Expression of tumor necrosis factor-α induced protein-8-like 2 in the development of T cells and its potential roles in the pathogenesis of asthma[J].Journal of Xinxiang Medical University,2022,39(12):1101-1106.[doi:10.7683/xxyxyxb.2022.12.001]
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肿瘤坏死因子α诱导蛋白8样分子2在T细胞发育过程中的表达及其对哮喘发病的潜在作用
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年12
页码:
1101-1106
栏目:
基础研究
出版日期:
2022-12-05

文章信息/Info

Title:
Expression of tumor necrosis factor-α induced protein-8-like 2 in the development of T cells and its potential roles in the pathogenesis of asthma
作者:
宋亚茹1; 田雪钦2; 3; 赵雨欣3; 宋苗苗3; 姜珊2; 3; 娄运伟2; 3; 王辉2; 3
（1.新乡医学院附属人民医院呼吸与危重症医学科二病区，河南　新乡　453000；2.新乡医学院医学检验学院，河南　新乡　453003；3.河南省免疫与靶向药物重点实验室，河南　新乡　453003）
Author(s):
SONG Yaru1; TIAN Xueqin2; 3; ZHAO Yuxin3; SONG Miaomiao2; JIANG Shan2; 3; LOU Yunwei2; 3; WANG Hui2; 3
(1.Department of Respiratory and Critical Care Medicine Second Ward,the Affiliated Remin Hospital of Xinxiang Medical University,Xinxiang 453000,Henan Province,China;2.School of Laboratory Medicine,Xinxiang Medical University,Xinxiang 453003,Henan Province,China;3.Henan Key Laboratory of Immunology and Targeted Drugs,Xinxiang Medical University,Xinxiang 453003,Henan Province,China)
关键词:
胸腺细胞; 肿瘤坏死因子α诱导蛋白8样分子2; 哮喘; 基因敲入
Keywords:
thymocytes; tumor necrosis factor-α inducible protein-8-like 2; asthma; gene knocking
分类号:
R562.2+5
DOI:
10.7683/xxyxyxb.2022.12.001
文献标志码:
A
摘要:
目的　探讨肿瘤坏死因子α诱导蛋白8样分子2（TIPE2）在T细胞发育过程中的表达及作用，分析其在哮喘发病中的潜在作用。方法　选择C57BL/6J雌性野生型（WT）小鼠、C57BL/6J雄性TIPE2基因敲除（Tipe2-/-）小鼠、C57BL/6J雄性绿色荧光蛋白敲入（Tipe2gfp/+）小鼠为研究对象。取WT和Tipe2gfp/+小鼠结肠组织和胸腺组织，获取肠道固有层淋巴细胞(LPLs)和胸腺细胞，采用流式细胞术检测结肠组织CD45-细胞、CD45+细胞及双阴性（DN）T细胞、双阳性（DP）T细胞、CD4+T细胞和CD8+ T细胞中TIPE2的表达。取WT和Tipe2-/-小鼠外周血、脾脏和肠系膜淋巴结，采用流式细胞术检测外周血、脾脏和肠系膜淋巴结中CD4+和CD8+T细胞水平。将10只Tipe2gfp/+小鼠随机分为对照组和哮喘组，每组5只。哮喘组小鼠以卵清蛋白诱导哮喘模型，对照组小鼠以生理盐水代替卵清蛋白诱导；采用流式细胞术检测2组小鼠肺泡灌洗液中CD4+T细胞和CD8+T细胞中TIPE2的表达。结果　WT和Tipe2gfp/+小鼠结肠组织LPLs中，大部分TIPE2+细胞表达免疫细胞的标志分子CD45，几乎所有的CD45-基质细胞不表达TIPE2。Tipe2gfp/+小鼠结肠组织中基质细胞和WT小鼠免疫细胞中检测不到TIPE2+细胞。Tipe2gfp/+小鼠胸腺组织DN T细胞中TIPE2相对表达量显著低于CD4+T细胞和CD8+ T细胞（t=53.312、8.230，P<0.01）；DP T细胞中TIPE2相对表达量显著低于CD4+T细胞和CD8+ T细胞（t=21.094、6.405，P<0.001）；DN T细胞中TIPE2相对表达量显著低于DP T细胞（t=7.619，P<0.01）；CD4+T细胞与CD8+ T细胞中TIPE2相对表达量比较差异无统计学意义（t=1.256，P>0.05）。WT小鼠与Tipe2-/-小鼠外周血、脾脏和淋巴结中CD4+T细胞百分比比较差异无统计学意义(t=0.670、0.128、0.128，P>0.05)；WT小鼠与Tipe2-/-小鼠外周血及脾脏和淋巴结中CD8+ T细胞百分比比较差异无统计学意义(t=1.488、0.542、0.255，P>0.05)。哮喘组小鼠肺泡灌洗液CD4+T细胞中TIPE2相对表达量显著低于对照组（t=15.370，P<0.001）；对照组与哮喘组小鼠肺泡灌洗液CD8+ T细胞中TIPE2相对表达量比较差异无统计学意义（t=0.132，P>0.05）。结论　在T细胞的不同发育阶段TIPE2的表达水平不同；TIPE2基因缺陷对T细胞的发育过程无明显影响，可显著影响哮喘发生发展过程中CD4+T细胞功能。
Abstract:
Objective　To investigate the the expression and role of tumor necrosis factor-α inducible protein 8 like molecule 2 (TIPE2) in the development of T cells,and analyze its potential role in the pathogenesis of asthma.Methods　C57BL/6J female wild-type(WT) mice,C57BL/6J male Tape2-/- mice,and C57BL/6J male Tape2gfp+ mice were selected as research objects.The colon tissue and thymus tissue of WT and Tipe2gfp/+mice were taken to obtain intestinal lamina propria lymphocytes (LPLs) and thymocytes.The expression of TIPE2 in CD45 cells,CD45+cells,double negative (DN) T cells,double positive (DP) T cells,CD4+T cells and CD8+T cells was detected by flow cytometry.The levels of CD4+ T cells and CD8+T cells in peripheral blood,spleen and mesenteric lymph nodes of WT and Tipe2-/- mice were detected by flow cytometry.A total of 10 Tipe2gfp/+ mice were divided into control group and asthma group,with 5 mice in each group.Asthma model of mice was induced by ovalbumin in the asthma group,and normal saline was replace ovalbumin in mice in the control group;the expression of TIPE2 in CD4+ T cells and CD8+ T cells in alveolar lavage fluid of mice in the two groups was detected by flow cytometry.Results　In the LPLs in colon tissues of WT and Tipe2gfp/+ mice,most TIPE2+ cells expressed the marker of immune cells CD45-,and almost all CD45- stromal cells did not express TIPE2.TIPE2+ cells were not detected in stroma cells in colon tissue of Tipe2gfp/+ mice and immune cells of WT mice.The relative expression level of TIPE2 in DN T cells was significantly lower than that in CD4+ T cells and CD8+ T cells in thymus of Tipe2gfp/+ mice (t=53.312,8.230;P<0.01);the relative expression level of TIPE2 in DP T cells was significantly lower than that in CD4+ T cells and CD8+ T cells (t=21.094,6.405;P<0.001);the relative expression level of TIPE2 in DN T cells was significantly lower than that in DP T cells (t=7.619,P<0.01);there was no significant difference in the relative expression level of TIPE2 between CD4+ T cells and CD8+ T cells (t=1.256,P>0.05).There was no significant difference in the percentage of CD4+ T cells in the peripheral blood,spleen and lymph nodes between WT mice and Tipe2-/- mice (t=0.670,0.128,0.128;P>0.05);there was no significant difference in the percentage of CD8+ T cells in the peripheral blood,spleen and lymph nodes between WT mice and Tipe2-/- mice (t=1.488,0.542,0.255;P>0.05).The relative expression level of TIPE2 in CD4+ T cells in alveolar lavage fluid of mice in the asthma group was significantly lower than that in the control group (t=15.370,P<0.001);there was no significant difference in the relative expression level of TIPE2 in CD8+ T cells of alveolar lavage fluid between the control group and asthma group (t=0.132,P>0.05).Conclusion　The expression level of TIPE2 are different in the different developmental stages of T cells.TIPE2 gene deficiency does not significantly affect the development of T cells,it can significantly affect the CD4+ T cells function in the pathogenesis of asthma.

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更新日期/Last Update: 2022-12-05