[1]白玉芬,徐洪涛,尹太勇,等.维生素D对系统性红斑狼疮鼠Peyer小结Tfh细胞微环境的影响[J].医学信息,2020,33(13):49-53.[doi:10.3969/j.issn.1006-1959.2020.13.014]
 BAI Yu-fen,XU Hong-tao,YIN Tai-yong,et al.The Effect of Vitamin D on the Microenvironment of Tfh Cells in Peyer’s Nodules of Systemic Lupus Erythematosus[J].Medical Information,2020,33(13):49-53.[doi:10.3969/j.issn.1006-1959.2020.13.014]
点击复制

维生素D对系统性红斑狼疮鼠Peyer小结Tfh细胞微环境的影响()
分享到:

医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
33卷
期数:
2020年13期
页码:
49-53
栏目:
论著
出版日期:
2020-07-01

文章信息/Info

Title:
The Effect of Vitamin D on the Microenvironment of Tfh Cells in Peyer’s Nodules of Systemic Lupus Erythematosus
文章编号:
1006-1959(2020)13-0049-05
作者:
白玉芬徐洪涛尹太勇
(解放军中部战区总医院儿科,湖北 武汉 430070)
Author(s):
BAI Yu-fenXU Hong-taoYIN Tai-yonget al
(Department of Pediatrics,Central War Theater General Hospital,Wuhan 430070,Hubei,China)
关键词:
维生素DSLE滤泡辅助性T细胞Peyer小结
Keywords:
Vitamin DSLEFollicular helper T cellsPeyer’s summary
分类号:
R692.3
DOI:
10.3969/j.issn.1006-1959.2020.13.014
文献标志码:
A
摘要:
目的 研究维生素D(VitD)在系统性红斑狼疮(SLE)治疗中的作用机制。方法 将6只C57/B6小鼠随机分为两组(组1、2),12只MRL/lpr小鼠随机分为四组(组3~6),每组3只,其中组1、6不做处理,组2:C57/B6小鼠+VitD[10 ng/(kg·d)];组3:MRL/lpr小鼠+VitD[10 ng/(kg·d)];组4:MRL/lpr小鼠+VitD[30 ng/(kg·d)];组5:MRL/lpr小鼠+VitD[10 ng/(kg·d)]+PA (0.8 μg/kg,3/W)。灌胃6周后处死小鼠,收集Peyer小结,流式细胞仪测定活化及凋亡的Tfh细胞百分率,B淋巴细胞及浆细胞百分率,趋化因子CCL12、CXCL13、CCL19、CCL21的表达;Real-Time PCR测定IL-21、IL-4mRNA的表达;Western Blot测定IL-21、IL-4、Bcl-6、Blimp-1、XBP-1、Pax-5、BAFF蛋白的表达。结果 与SLE鼠组相比,给予VitD可以降低Tfh细胞百分率但不能明显改变Tfh细胞的活化,减少细胞凋亡,降低B淋巴细胞和浆细胞百分率。同时可以下调IL-21、IL-4、Blimp-1、XBP-1、BAFF蛋白,细胞因子IL-21、IL-4mRNA和趋化因子CCL12、CXCL13、CCL19、CCL21的表达,上调Bcl-6、Pax-5蛋白的表达,且呈剂量依赖性,与PA联用效果更佳。结论 VitD与其受体结合可能通过抑制Tfh细胞、相关因子及微环境、抑制自身免疫抗体的生成,从而对SLE产生治疗作用。
Abstract:
Objective To study the mechanism of vitamin D (VitD) in the treatment of systemic lupus erythematosus (SLE).Methods Six C57/B6 mice were randomly divided into two groups (groups 1 and 2), and 12 MRL/lpr mice were randomly divided into four groups (groups 3 to 6), with 3 mice in each group, of which groups 1 and 6 without treatment, Group 2: C57/B6 mice + VitD[10 ng/(kg·d)]; Group 3: MRL/lpr mice+VitD[10 ng/(kg·d)]; Group 4: MRL /lpr mice+VitD[30 ng/(kg·d)]; Group 5: MRL/lpr mice+VitD[10 ng/(kg·d)]+PA (0.8 μg/kg, 3/W). After 6 weeks of gavage, the mice were sacrificed, Peyer nodules were collected, flow cytometry was used to determine the percentage of activated and apoptotic Tfh cells, B lymphocytes and plasma cells, and the expression of chemokines CCL12, CXCL13, CCL19, CCL21; Real-Time PCR measured the expression of IL-21 and IL-4 mRNA; Western Blot measured the expression of IL-21, IL-4, Bcl-6, Blimp-1, XBP-1, Pax-5 and BAFF protein.Results Compared with the SLE mice group, the administration of VitD can reduce the percentage of Tfh cells but can not significantly change the activation of Tfh cells, reduce apoptosis, and reduce the percentage of B lymphocytes and plasma cells. At the same time, it can down-regulate the expression of IL-21, IL-4, Blimp-1, XBP-1, BAFF protein, cytokines IL-21, IL-4mRNA and chemokines CCL12, CXCL13, CCL19, CCL21, and up-regulate Bcl-6,the expression of Pax-5 protein is dose-dependent, and it is more effective in combination with PA.Conclusion The binding of VitD to its receptor may have a therapeutic effect on SLE by inhibiting Tfh cells, related factors and microenvironment, and inhibiting the production of autoimmune antibodies.

参考文献/References:

[1]曹平,赵玉,王静.系统性红斑狼疮分子病因研究进展[J].中国免疫学杂志,2013,29(6):657-661.[2]滕菲,关尚琪,梅轶芳,等.系统性红斑狼疮相关肺动脉高压的发病机制及治疗研究进展[J].中华医学杂志,2018,98(17):1371-1373.[3]Pedro EM,Flor DRFSL,Scavuzzi BM,et al.Trace Elements Associated with Systemic Lupus Erythematosus and Insulin Resistance[J].Biological Trace Element Research,2019,191(1):34-44.[4]Dhar JP,Essenmacher L,Dhar R,et al.The Effect of History of Abnormal Pap Smear or Preceding HPV infection on the Humoral Immune Response to Quadrivalent Human Papilloma virus(qHPV)Vaccine in Women with Systemic Lupus Erythematosus[J].Human Vaccines&Immunotherapeutics, 2018,14(9):2318-2322.[5]吴芳.滤泡辅助性T细胞参与实验性自身免疫性脑脊髓炎的初步研究[D].第四军医大学,2014.[6]陈升,李杨磊,王元元.滤泡辅助性T细胞的研究进展[J].蚌埠医学院学报,2019,44(1):138-141.[7]高筱斐,赵明.microRNA-21对系统性红斑狼疮滤泡样辅助T细胞异常分化的调控作用[C]//第十三届全国免疫学学术大会摘要汇编.2018.[8]褚阳.滤泡辅助性T细胞在类风湿关节炎滑膜中的表达及鉴定[D].苏州大学,2014.[9]蔡茂文,张晶,周彬.类风湿关节炎与系统性红斑狼疮患者甲状腺功能的比较分析[J].实用医院临床杂志,2013,10(3):80-82.[10]石娴,石年,解翠林,等.特应性皮炎患者血清VitD、tIgE、IL-4和IL-6水平检测及临床意义[J].检验医学与临床,2017,14(24):3605-3606.[11]Amir E,Cecchini RS,Ganz PA,et al.25-hydroxy vitamin D(VitD)and associated variables as predictors of breast cancer(BC)risk and tamoxifen benefit in NSABP-P1[J].Breast Cancer Research&Treatment,2012,135(3):923-923.[12]Tuomainen TP,Virtanen JK,Voutilainen S,et al.Glucose Metabolism Effects of Vitamin D in Prediabetes:The VitDmet Randomized Placebo-Controlled Supplementation Study[J].J Diabetes Res,2015(2015):672653.[13]孟庆军,华青,戴婷婷.儿童血清25(OH)VitD与骨代谢标志物水平的相关性研究[J].海南医学院学报,2015,21(10):1390-1392.[14]沈佩芳,田军,丁晓玲.血清维生素D水平与支气管哮喘患儿病情严重程度的相关性[J].浙江临床医学,2018,20(7):1190-1192.[15]王颖,卢美萍,滕丽萍,等.血清25羟维生素D3水平与幼年特发性关节炎的关系[C]//2015年浙江省医学会儿科学分会学术年会暨儿内科疾病诊治新进展国家级继续教育学习班.2015.[16]吴冬梅,刘培成.维生素D与老年骨质疏松[J].中国骨质疏松杂志,2015(5):634-637.[17]维生素D受体在炎性肌病的发病作用及维生素D的干预研究[D].南开大学,2014.[18]Vincent FB,Morand EF,Schneider P,et al.The BAFF/APRIL system in SLE pathogenesis[J].Nature Reviews Rheumatology,2014,10(6):365-373.[19]段春巧,杨雯雯,雷玲彦,等.Bcl-6/Blimp-1/IL-21在原发性干燥综合征中的致病作用[J].中国免疫学杂志,2015(3):384-388,392.[20]Zhang XY,Ma ZP,Cui WL,et al.Potential mechanism and prognostic value of promoter methylation of PRDM1 gene in diffuse large B cell lymphoma[J].Chinese Journal of Pathology,2016,45(12):831-837.[21]Yeol SG,Won YS,Kim YI,et al.Decreased Bcl-6 and increased Blimp-1 in the peritoneal cavity of patients with endometriosis[J].Clinical&Experimental Obstetrics&Gynecology,2015,42(2):156.[22]Chaves AC,Cerávolo IP,Gomes JA,et al.IL-4 and IL-13 regulate the induction of indoleamine 2,3-dioxygenase activity and the control of Toxoplasma gondii replication in human fibroblasts activated with IFN-gamma[J].European Journal of Immunology,2015,31(2):333-344.[23]An LF,Zhang XH,Sun XT,et al.Unexplained infertility patients have increased serum IL-2,IL-4,IL-6,IL-8,IL-21,TNFα,IFNγ and increased Tfh/CD4 T cell ratio: increased Tfh and IL-21 strongly correlate with presence of autoantibodies[J].Immunological Investigations,2015,44(2):1-10.[24]Botti E,Boca AN,Spallone G,et al.The Role of IL-21 in Chronic Inflammatory Skin Diseases[J].Current Dermatology Reports,2013,2(1):11-17.[25]孙青,吴昌平,蒋敬庭.趋化因子及其受体在肿瘤免疫中调节作用的新进展[J].中国医药生物技术,2015,10(4):294-296.[26]Jiang BC,Cao DL,Zhang X,et al.CXCL13 drives spinal astrocyte activation and neuropathic pain via CXCR5[J].Journal of Clinical Investigation,2016,126(2):745-761.[27]Wu B,Wang W,Zhan Y,et al.CXCL13,CCL4,and sTNFR as circulating inflammatory cytokine markers in primary and SLE-related autoimmune hemolytic anemia[J].Journal of Translational Medicine,2015,13(1):112.[28]艾汐汐.CD5+B细胞在类风湿关节炎、系统性红斑狼疮、干燥综合征患者外周血中表达的临床意义的探讨[D].中国医科大学,2015.[29]Mills SC,Howell L,Beekman A,et al.Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4[J].Cellular Signalling,2017(42):88-96.[30]Deleon-Pennell KY,Iyer RP,Ero OK,et al.Periodontal-induced chronic inflammation triggers macrophage secretion of Ccl12 to inhibit fibroblast-mediated cardiac wound healing[J].Jci Insight,2017,2(18):e94207.[31]Marazioti A,Kairi C A,Spella M,et al.Beneficial Impact of CCL2 and CCL12 Neutralization on Experimental Malignant Pleural Effusion[J].PloS One,2013,8(8):e71207.[32]蔡文芝.趋化因子CCL19和CCL21及其受体CCR7与冠心病的关联研究及功能分析[J].中国循环杂志,2014(z1):29-29.[33]Hansen M,Ozcan Met,Larsen NB,et al.Autocrine CCL19 blocks dendritic cell migration toward weak gradients of CCL21[J].Cytotherapy,2016,18(9):1187-1196.

相似文献/References:

[1]哈海枫,严鹏仲.高原人群维生素D水平的影响因素分析[J].医学信息,2022,35(12):126.[doi:10.3969/j.issn.1006-1959.2022.12.030]
 HA Hai-feng,YAN Peng-zhong.Analysis on Influencing Factors of Vitamin D Level in Plateau Population[J].Medical Information,2022,35(13):126.[doi:10.3969/j.issn.1006-1959.2022.12.030]
[2]付庆萍,黄万秀,李 毅.维生素D水平与成人哮喘及非哮喘的相关性研究[J].医学信息,2019,32(05):87.[doi:10.3969/j.issn.1006-1959.2019.05.026]
 FU Qin-ping,HUANG Wang-xiu,LI Yi.Correlation between Vitamin D Levels and Adult Asthma and Non-asthma[J].Medical Information,2019,32(13):87.[doi:10.3969/j.issn.1006-1959.2019.05.026]
[3]左俊芳,刘沙沙,崔洪艳.妊娠期糖尿病高危因素及预防措施研究[J].医学信息,2022,35(17):177.[doi:10.3969/j.issn.1006-1959.2022.17.048]
 ZUO Jun-fang,LIU Sha-sha,CUI Hong-yan.Study on High Risk Factors and Preventive Measures of Gestational Diabetes Mellitus[J].Medical Information,2022,35(13):177.[doi:10.3969/j.issn.1006-1959.2022.17.048]
[4]王文建,王博韬,李昊辰,等.维生素D辅助股骨近端防旋髓内钉内固定治疗老年股骨转子间骨折的远期疗效观察[J].医学信息,2022,35(14):119.[doi:10.3969/j.issn.1006-1959.2022.14.029]
 WANG Wen-jian,WANG Bo-tao,LI Hao-chen,et al.Long-term Effect of Vitamin D Assisted Proximal Femoral Nail Anti-rotation Internal Fixation in the Treatment of Elderly Patients with Intertrochanteric Fracture of Femur[J].Medical Information,2022,35(13):119.[doi:10.3969/j.issn.1006-1959.2022.14.029]
[5]黄 铃,孙 冰,蔡金美,等.维生素D治疗川崎病的疗效及其对血清促炎因子的影响[J].医学信息,2019,32(18):81.[doi:10.3969/j.issn.1006-1959.2019.18.025]
 HUANG Ling,SUN Bing,CAI Jin-mei,et al.Therapeutic Effect of Vitamin D on Kawasaki Disease and Its Effect on Serum Pro-inflammatory Factors[J].Medical Information,2019,32(13):81.[doi:10.3969/j.issn.1006-1959.2019.18.025]
[6]张正超,李毓龙,贺 腊,等.2019年简阳地区儿童维生素D营养状况调查[J].医学信息,2020,33(11):131.[doi:10.3969/j.issn.1006-1959.2020.11.041]
 ZHANG Zheng-chao,LI Yu-long,HE La,et al.2019 Survey of Vitamin D Nutrition Status of Children in Jianyang District[J].Medical Information,2020,33(13):131.[doi:10.3969/j.issn.1006-1959.2020.11.041]
[7]杨茜岚,相东晓,谢 丹,等.维生素A,D,E与儿童反复呼吸道感染关系的研究[J].医学信息,2023,36(21):66.[doi:10.3969/j.issn.1006-1959.2023.21.014]
 YANG Xi-lan,XIANG Dong-xiao,XIE Dan,et al.Study on the Correlation Between Vitamin A, D, E and Recurrent Respiratory Tract Infection in Children[J].Medical Information,2023,36(13):66.[doi:10.3969/j.issn.1006-1959.2023.21.014]
[8]郑鑫辉,崔慧丽,杨铁毅,等.粪乳铁蛋白、维生素D水平与克罗恩病患者骨质疏松的相关性[J].医学信息,2021,34(05):114.[doi:10.3969/j.issn.1006-1959.2021.05.032]
 ZHENG Xin-hui,CUI Hui-li,YANG Tie-yi,et al.Correlation Between Fecal Lactoferrin,Vitamin D Levels and Osteoporosis in Crohn’s Disease[J].Medical Information,2021,34(13):114.[doi:10.3969/j.issn.1006-1959.2021.05.032]
[9]张 萌,杨利琦.中枢性性早熟女童维生素D水平分析[J].医学信息,2023,36(04):108.[doi:10.3969/j.issn.1006-1959.2023.04.021]
 ZHANG Meng,YANG Li-qi.Analysis of Vitamin D Levels in Girls with Central Precocious Puberty[J].Medical Information,2023,36(13):108.[doi:10.3969/j.issn.1006-1959.2023.04.021]
[10]王翠静,朱艳红,刘凤芝.维生素D联合门冬胰岛素对妊娠期糖尿病患者糖脂代谢、胰岛素抵抗的影响[J].医学信息,2023,36(07):131.[doi:10.3969/j.issn.1006-1959.2023.07.025]
 WANG Cui-jing,ZHU Yan-hong,LIU Feng-zhi.Effects of Vitamin D Combined with Insulin Aspart on Glucose and Lipid Metabolism and Insulin Resistance in Patients with Gestational Diabetes Mellitus[J].Medical Information,2023,36(13):131.[doi:10.3969/j.issn.1006-1959.2023.07.025]

更新日期/Last Update: 1900-01-01