Fyn在母胎界面的表达及免疫调控作用

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摘要目的研究Fyn在母胎界面的表达及作用。方法构建妊娠和自然流产小鼠模型,免疫组化、实时荧光定量PCR、western-blot检测子宫胎盘组织中Fyn表达;建立LPS诱导的小鼠流产模型,以Fyn活性抑制剂,计算胚胎吸收率,实时荧光定量PCR和流式细胞学技术检测炎症因子(IL-17、RORγt、IFN-γ和TNF-α)水平、Th17和Treg细胞含量。结果 Fyn水平在小鼠妊娠第4.5天最高,着床后明显降低;Fyn主要表达于子宫系膜淋巴聚集区的淋巴细胞中,自然流产组Fyn表达高于正常妊娠组;SU6656抑制LPS诱导的小鼠流产和IL-17、RORγt、TNF-α的异常高表达,以及Th17细胞含量的升高。结论 Fyn通过Th17细胞等免疫因素参与母胎免疫调控及妊娠维持。

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	刘倩
	杨菁

关键词 ：母胎免疫, 自然流产, 免疫耐受, 酪氨酸激酶, Th17细胞

Abstract：Objective To observe Fyn expression at the fetomaternal interface and its potential roles. Methods Murine models of normal pregnant and immunological abortion were established. Immunohistochemistry, real time quantitative PCR (qPCR) and western-blotting were applied to analyze Fyn expression in uteroplacental complexes; LPS was performed to induce immune imbalance and abortion of mice, selective Fyn inhibitor (SU6656) was injected simultaneously. The rates of fetal resorption were calculated, the mRNA levels of IL-17, RORγt, IFN-γ and TNF-α were examined through qPCR, and the percentages of Tregs and Th17 cells in CD4+ lymphocyte of uteroplacental tissues were evaluated by flow cytometry. Results Fyn level was highest among mice at E4.5, and then declined sharply after implantation, Fyn was expressed mainly by lymphocytes in mesometrial lymphoid aggregate of pregnancy. Compared to normal pregnant mice, the levels of Fyn were higher in abortive model mice; SU6656 rescued LPS-induced miscarriage and immunological imbalance at the fetomaternal interface. It inhibited the increased levels of cytokines (IL-17, RORγt and TNF-α) and proportion of Th17 cells induced by LPS. Conclusion Fyn plays pivotal roles in pregnancy, through regulating maternal-fetal immunity, particularly Th17 cell differentiation and function.

Key words： maternal-fetal immunity spontaneous abortion immunity tolerance tyrosine kinase Th17 cell

收稿日期: 2021-02-19

ZTFLH:

R71

基金资助:国家自然科学基金青年项目(8180061643)

通讯作者: 杨菁(13507182023@163.com)

引用本文:

刘倩, 杨菁. Fyn在母胎界面的表达及免疫调控作用[J]. 中国生育健康杂志, 2022, 33(1): 27-32. LIU Qian, YANG Jing. The expression of Fyn at the fetomaternal interface and its roles in pregnancy immunity. Chinese Journal of Reproductive Health, 2022, 33(1): 27-32.

链接本文:

http://cjrh.bjmu.edu.cn/CN/ 或 http://cjrh.bjmu.edu.cn/CN/Y2022/V33/I1/27

1 Saminathan H,Charli A,Luo J,et al.Fyn kinase mediates pro-inflammatory response in a mouse model of endotoxemia:Relevance to translational research.Eur J Pharmacol,2020,881:173-259.
2 Paranjape A,Haque TT,Kiwanuka KN,et al.The Fyn-Stat5 cascade is required for Fcγ receptor-mediated mast cell function.Cell Immunol,2020,356:104-134.
3 Ueda A,Zhou L,Stein P L.Fyn promotes Th17 differentiation by regulating the kinetics of RORgammat and Foxp3 expression.J Immunol,2012,188:5247-5256.
4 刘倩,林羿,张珺,等.干扰素调节因子4在母胎界面的表达特点及作用.中华生物医学工程杂志,2016,22:392-397.
5 Papúchová H,Meissner TB,Li Q,et al.The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface.Front Immunol,2019,10:27-30.
6 Muyayalo KP,Li ZH,Mor G,et al.Modulatory effect of intravenous immunoglobulin on Th17/Treg cell balance in women with unexplained recurrent spontaneous abortion.Am J Reprod Immunol,2018,80:e13018.
7 Bouza AA,Philippe JM,Edokobi N,et al.Sodium channel β1 subunits are post-translationally modified by tyrosine phosphorylation,S-palmitoylation,and regulated intramembrane proteolysis.J Biol Chem,2020,295:10380-10393.
8 Mukherjee A,Singh R,Udayan S,et al.A Fyn biosensor reveals pulsatile,spatially localized kinase activity and signaling crosstalk in live mammalian cells.Elife,2020,9:e50571.
9 Grossman H,Har-Paz E,Gindi Net al.Regulation of GVBD in mouse oocytes by miR-125a-3p and Fyn kinase through modulation of actin filaments.Sci Rep,2017,7:22-38.
10 Maldonado-García D,Salgado-Lucio ML,Roa-Espitia AL,et al.Calpain inhibition prevents flotillin re-ordering and Src family activation during capacitation.Cell Tissue Res,2017,369:395-412.
11 Sharma N,Akhade AS,Qadri A.Src kinases central to T-cell receptor signaling regulate TLR-activated innate immune responses from human T cells.Innate Immun,2016,22:238-244.
12 Wang S,Li M,Sun F,Chen C,Ye J,Li D,Qian J,Du M.Th17/Treg-cell balance in the peripheral blood of pregnant females with a history of recurrent spontaneous abortion receiving progesterone or cyclosporine A.Exp Ther Med,2021,21:37.
13 Qian J,Zhang N,Lin J,et al.Distinct pattern of Th17/Treg cells in pregnant women with a history of unexplained recurrent spontaneous abortion.Biosci Trends,2018,12:157-167.
14 Panicker N,Saminathan H,Jin H,et al.Fyn Kinase Regulates Microglial Neuroinflammatory Responses in Cell Culture and Animal Models of Parkinson's Disease.J Neurosci,2015,35:10058-10077.
15 Xu WM,Xiao ZN,Wang XB,IL-17 Induces Fetal Loss in a CBA/J×BALB/c Mouse Model,and an Anti-IL-17 Antibody Prevents Fetal Loss in a CBA/J×DBA/2 Mouse Model.Am J Reprod Immunol,2016,75:51-58.
16 Li W,Geng L,Liu X,et al.Recombinant adioonectin alleviates abortion in mice by regulating Th17/Treg imbalance via p38MARK-STAT5 pathway.Biol Reprod,2019,100:1008-1017.
17 Wang W J,Liu F J,Xin-Liu,et al.Adoptive transfer of pregnancy-induced CD4+CD25+ regulatory T cells reverses the increase in abortion rate caused by interleukin 17 in the CBA/JxBALB/c mouse model.Hum Reprod,2014,29:946-952.
18 Li L,Tu J,Jiang Y,et al.Regulatory T cells decrease invariant natural killer T cell-mediated pregnancy loss inmiceJ.Mucosal Immunol,2017,10:613-623.
19 Walker C,Ghazisaeidi S,Collet B,Boisvert A,Culty M.In utero exposure to low doses of genistein and di-(2-ethylhexyl) phthalate (DEHP) alters innate immune cells in neonatal and adult rat testes.Andrology,2020,8:943-964.
20 Chavez-Solano M,Ibarra-Sanchez A,Trevino M,et al.Fyn kinase genetic ablation causes structural abnormalities in mature retina and defective Muller cell function.Mol CellNeurosci,2016,72:91-100.