留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

CD38影响Treg/Th17平衡促进类风湿关节炎发生发展的机制研究

林海丽 杜孝康 王依璐 蔡成松 高锦 潘峰

林海丽, 杜孝康, 王依璐, 蔡成松, 高锦, 潘峰. CD38影响Treg/Th17平衡促进类风湿关节炎发生发展的机制研究[J]. 中华全科医学, 2024, 22(1): 18-20. doi: 10.16766/j.cnki.issn.1674-4152.003321
引用本文: 林海丽, 杜孝康, 王依璐, 蔡成松, 高锦, 潘峰. CD38影响Treg/Th17平衡促进类风湿关节炎发生发展的机制研究[J]. 中华全科医学, 2024, 22(1): 18-20. doi: 10.16766/j.cnki.issn.1674-4152.003321
LIN Haili, DU Xiaokang, WANG Yilu, CAI Chengsong, GAO Jin, PAN Feng. CD38 influences Treg/Th17 balance to promote rheumatoid arthritis[J]. Chinese Journal of General Practice, 2024, 22(1): 18-20. doi: 10.16766/j.cnki.issn.1674-4152.003321
Citation: LIN Haili, DU Xiaokang, WANG Yilu, CAI Chengsong, GAO Jin, PAN Feng. CD38 influences Treg/Th17 balance to promote rheumatoid arthritis[J]. Chinese Journal of General Practice, 2024, 22(1): 18-20. doi: 10.16766/j.cnki.issn.1674-4152.003321

CD38影响Treg/Th17平衡促进类风湿关节炎发生发展的机制研究

doi: 10.16766/j.cnki.issn.1674-4152.003321
基金项目: 

国家自然科学基金项目 81701568

详细信息
    通讯作者:

    潘峰,E-mail:panfeng1240@126.com

  • 中图分类号: R593.22  R-332

CD38 influences Treg/Th17 balance to promote rheumatoid arthritis

  • 摘要:   目的  检测类风湿关节炎(RA)小鼠模型组织中分化簇38(CD38)的表达和CD4+T细胞中调节性T细胞(Tregs)与辅助性T细胞17(Th17)的比例,探讨CD38促进RA发生发展的机制。  方法  构建胶原诱导小鼠关节炎模型(CIA),每组3只,通过蛋白免疫印迹、荧光定量PCR检测滑膜组织、脾脏、淋巴结中CD38蛋白、mRNA的表达;采用流式细胞术分析Th17细胞和Treg细胞的比例;从小鼠脾脏分离出幼稚CD4+T细胞,分化后,检测CD38蛋白的表达,计算Th17细胞和Treg细胞的比例;极化幼稚CD4+T细胞,检测PI3K、AKT、p-AKT、mTOR、p-mTOR的蛋白表达,分析CD38对PI3K/AKT/mTOR信号通路的影响。  结果  CIA中各滑膜组织、脾脏、淋巴结中CD38蛋白表达高于对照组,差异均有统计学意义(P<0.01);与极化组+sh-NC相比,极化组+sh-CD38的Th17细胞比例降低,Treg细胞比例升高(P<0.01);p-AKT、p-mTOR蛋白表达量在极化组+sh-NC(3.00±0.08、3.18±0.12)均高于极化组+sh-CD38(2.48±0.09、1.70±0.10,P<0.01)。  结论  CD38在CIA中高表达,抑制CD38的表达CIA炎症得到改善;在特定分化条件下,CD38高表达使得Th17细胞比例升高,Treg细胞比例下降;经极化处理,CD38能通过PI3K/AKT/mTOR信号通路影响Treg/Th17平衡促进类风湿关节炎炎症的发生发展。

     

  • 表  1  类风湿关节炎小鼠模型不同组织中CD38蛋白的表达水平(x±s)

    Table  1.   Expression levels of CD38 protein in different tissues of rheumatoid arthritis mice model(x±s)

    组别 只数 关节滑膜 脾脏 淋巴结
    对照组 3 0.50±0.03 0.71±0.05 0.78±0.03
    模型组 3 0.73±0.04a 1.09±0.05a 1.26±0.07a
    模型组+sh-NC 3 0.70±0.02 1.11±0.08 1.23±0.03
    模型组+sh-CD38 3 0.32±0.03b 0.51±0.03b 0.60±0.03b
    F 70.865 52.841 123.364
    P <0.001 <0.001 <0.001
    注:与对照组比较,aP<0.001;与模型组+sh-NC比较,bP<0.001。
    下载: 导出CSV

    表  2  类风湿关节炎小鼠模型不同组织中CD38 mRNA的表达水平(x±s)

    Table  2.   Expression levels of CD38 mRNA in different tissues of rheumatoid arthritis mice model(x±s)

    组别 只数 关节滑膜 脾脏 淋巴结
    对照组 3 1.01±0.17 1.00±0.14 1.00±0.09
    模型组 3 1.53±0.06a 1.62±0.09a 1.68±0.09a
    模型组+sh-NC 3 1.62±0.06 1.68±0.09 1.74±0.10
    模型组+sh-CD38 3 1.26±0.05b 1.33±0.06b 1.45±0.09b
    F 24.286 28.816 39.583
    P <0.001 <0.001 <0.001
    注:与对照组比较,aP<0.001;与模型组+sh-NC比较,bP<0.001。
    下载: 导出CSV

    表  3  类风湿关节炎小鼠模型脾脏中Th17、Treg及Treg/Th17细胞比例比较(x±s)

    Table  3.   Changes in the ratio of Treg/Th17 cells in the spleen of mice model of rheumatoid arthritis(x±s)

    组别 只数 Th17(%) Treg(%) Treg/Th17
    对照组 3 4.33±0.50 8.35±0.28 1.94±0.16
    模型组 3 9.11±0.22a 2.85±0.12a 0.31±0.02a
    模型组+sh-NC 3 9.10±0.38 3.08±0.11 0.34±0.03
    模型组+sh-CD38 3 7.12±0.17b 5.31±0.28b 0.83±0.04b
    F 130.498 436.264 235.754
    P <0.001 <0.001 <0.001
    注:与对照组比较,aP<0.05;与模型组+sh-NC比较,bP<0.05。
    下载: 导出CSV

    表  4  幼稚CD4+ T细胞极化处理后CD38的表达水平(x±s)

    Table  4.   Expression levels of CD38 in polarized CD4+ T cells(x±s)

    组别 只数 CD38
    对照组 3 1.00±0.05
    极化组 3 1.63±0.06a
    极化组+sh-NC 3 1.69±0.09
    极化组+sh-CD38 3 1.28±0.05b
    F 140.562
    P <0.001
    注:与对照组比较,aP<0.01;与极化组+sh-NC比较,bP<0.01。
    下载: 导出CSV

    表  5  CD4+ T细胞极化后Th17、Treg及Treg/Th17细胞比例的变化(x±s)

    Table  5.   Changes in Treg/Th17 cell ratio after CD4+ T cell polarization(x±s)

    组别 只数 Th17(%) Treg(%) Treg/Th17
    对照组 3 0.88±0.18 23.20±0.53 27.00±5.48
    极化组 3 5.52±0.43a 17.97±0.99a 3.10±0.40a
    极化组+sh-NC 3 5.10±0.47 18.40±0.56 3.62±0.23
    极化组+sh-CD38 3 2.01±0.13b 20.83±0.45b 10.37±0.45b
    F 136.469 51.182 48.950
    P <0.001 <0.001 <0.001
    注:与对照组比较,aP<0.05;与极化组+sh-NC比较,bP<0.05。
    下载: 导出CSV

    表  6  CD4+ T细胞极化后p-AKT的蛋白表达水平(x±s)

    Table  6.   p-AKT protein expression after CD4+ T cell polarisation

    组别 只数 p-AKT p-AKT/AKT p-mTOR p-mTOR/mTOR
    对照组 3 1.00±0.06 1.00±0.06 1.00±0.03 1.00±0.11
    极化组 3 3.08±0.08a 3.08±0.12a 3.01±0.02a 2.98±0.13a
    极化组+sh-NC 3 3.00±0.08 2.97±0.16 3.18±0.12 2.83±0.07
    极化组+sh-CD38 3 2.48±0.09b 2.62±0.15b 1.70±0.10b 1.54±0.14b
    F 454.545 166.347 456.507 212.903
    P <0.001 <0.001 <0.001 <0.001
    注:与对照组比较,aP<0.05;与极化组+sh-NC比较,bP<0.05。
    下载: 导出CSV
  • [1] SPARKS J A. Rheumatoid arthritis[J]. Ann Intern Med, 2019, 170(1): Itc1-itc16. DOI: 10.7326/aitc201901010.
    [2] SMITH M H, BERMAN J R. What is rheumatoid arthritis?[J]. JAMA, 2022, 327(12): 1194. doi: 10.1001/jama.2022.0786
    [3] 王涛, 李志军. 类风湿关节炎的诊断与治疗[J]. 中华全科医学, 2020, 18(2): 170-171. http://www.zhqkyx.net/article/id/db5b4b90-cd84-4faf-aea9-553bd1709ec4

    WANG T, LI Z J. Diagnosis and treatment of rheumatoid arthritis[J]. Chinese Journal of General Practice, 2020, 18(2): 170-171. http://www.zhqkyx.net/article/id/db5b4b90-cd84-4faf-aea9-553bd1709ec4
    [4] LIN Y J, ANZAGHE M, SCHVLKE S. Update on the pathomechanism, diagnosis, and treatment options for rheumatoid arthritis[J]. Cells, 2020, 9(4): 880. doi: 10.3390/cells9040880
    [5] JANG S, KWON E J, LEE J J. Rheumatoid arthritis: pathogenic roles of diverse immune cells[J]. Int J Mol Sci, 2022, 23(2): 905. doi: 10.3390/ijms23020905
    [6] LEE G R. The balance of Th17 versus Treg cells in autoimmunity[J]. Int J Mol Sci, 2018, 19(3): 730. doi: 10.3390/ijms19030730
    [7] YAN J B, LUO M M, CHEN Z Y, et al. The function and role of the Th17/Treg cell balance in inflammatory bowel disease[J]. J Immunol Res, 2020, 2020: 8813558. DOI: 10.1155/2020/8813558.
    [8] XU M, POKROVSKII M, DING Y, et al. c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont[J]. Nature, 2018, 554(7692): 373-377. doi: 10.1038/nature25500
    [9] VAN RAEMDONCK K, UMAR S, PALASIEWICZ K, et al. CCL21/CCR7 signaling in macrophages promotes joint inflammation and Th17-mediated osteoclast formation in rheumatoid arthritis[J]. Cell Mol Life Sci, 2020, 77(7): 1387-1399. doi: 10.1007/s00018-019-03235-w
    [10] PIEDRA-QUINTERO Z L, WILSON Z, NAVA P, et al. CD38: an immunomodulatory molecule in inflammation and autoimmunity[J]. Front Immunol, 2020, 11: 597959. DOI: 10.3389/fimmu.2020.597959.
    [11] CHINI C C S, PECLAT T R, WARNER G M, et al. CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD(+) and NMN levels[J]. Nat Metab, 2020, 2(11): 1284-1304. doi: 10.1038/s42255-020-00298-z
    [12] FENG F B, QIU H Y. Effects of Artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway in rat models with rheumatoid arthritis[J]. Biomed Pharmacother, 2018, 102: 1209-1220. doi: 10.1016/j.biopha.2018.03.142
    [13] FLAHERTY S, REYNOLDS J M. Mouse naive CD4+ T cell isolation and in vitro differentiation into T cell subsets[J]. J Vis Exp, 2015(98): 52739. DOI: 10.3791/52739.
    [14] RADU A F, BUNGAU S G. Management of rheumatoid arthritis: an overview[J]. Cells, 2021, 10(11): 2857. DOI: 10.3390/cells10112857.
    [15] CONFORTI A, DI COLA I, PAVLYCH V, et al. Beyond the joints, the extra-articular manifestations in rheumatoid arthritis[J]. Autoimmun Rev, 2021, 20(2): 102735. DOI: 10.1016/j.autrev.2020.102735.
    [16] CHANG X, YUE L, LIU W, et al. CD38 and E2F transcription factor 2 have uniquely increased expression in rheumatoid arthritis synovial tissues[J]. Clin Exp Immunol, 2014, 176(2): 222-231. doi: 10.1111/cei.12268
    [17] WANG H, FANG K, YAN W, et al. T-cell immune imbalance in rheumatoid arthritis is associated with alterations in NK cells and NK-like T cells expressing CD38[J]. J Innate Immun, 2022, 14(2): 148-166. doi: 10.1159/000516642
    [18] AMICI S A, YOUNG N A, NARVAEZ-MIRANDA J, et al. CD38 is robustly induced in human macrophages and monocytes in inflammatory conditions[J]. Front Immunol, 2018, 9: 1593. DOI: 10.3389/fimmu.2018.01593.
    [19] COLE S, WALSH A, YIN X, et al. Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus[J]. Arthritis Res Ther, 2018, 20(1): 85. doi: 10.1186/s13075-018-1578-z
    [20] FERGUSON I D, GRIFFIN P, MICHEL J J, et al. T cell receptor-independent, CD31/IL-17A-driven inflammatory axis shapes synovitis in juvenile idiopathic arthritis[J]. Front Immunol, 2018, 9: 1802. DOI: 10.3389/fimmu.2018.01802.
    [21] LIU K, ZHANG Y, LIU L, et al. miR-125 regulates PI3K/Akt/mTOR signaling pathway in rheumatoid arthritis rats via PARP2[J]. Biosci Rep, 2019, 39(1): BSR20180890. DOI: 10.1042/BSR20180890.
    [22] CHENG Q, CHEN M, LIU M, et al. Semaphorin 5A suppresses ferroptosis through activation of PI3K-AKT-mTOR signaling in rheumatoid arthritis[J]. Cell Death Dis, 2022, 13(7): 608. doi: 10.1038/s41419-022-05065-4
    [23] CHEN K, LIN Z W, HE S M, et al. Metformin inhibits the proliferation of rheumatoid arthritis fibroblast-like synoviocytes through IGF-IR/PI3K/AKT/m-TOR pathway[J]. Biomed Pharmacother, 2019, 115: 108875. DOI: 10.1016/j.biopha.2019.108875.
  • 加载中
表(6)
计量
  • 文章访问数:  339
  • HTML全文浏览量:  96
  • PDF下载量:  19
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-04-29
  • 网络出版日期:  2024-03-09

目录

    /

    返回文章
    返回