调节性T细胞在动脉硬化中的作用与机制的进展
摘要
<正>动脉硬化性疾病是世界范围内造成死亡的重要原因,2017年,我国现患冠心病人群达1 100万,并且呈持续上升阶段,死亡率也在持续走高~([1])。已有日益增多的证据表明动脉粥样硬化(atherosclerosis,As)是由免疫介导的动脉壁的炎症性疾病,其中T细胞介导的免疫应答在As病变形成过程中起重要作用~([2,3])。调节性T细胞(T regulatory cells,Tregs)因其具有调节每个免疫细胞的功能,成为外周免疫耐受和稳态的基石,其
引文
[1] 陈伟伟,高润霖,刘力生,等.《中国心血管病报告2017》概要[J].中国循环杂志,2018,33(1):1-8.
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[4] Long S A,Buckner J H.CD4+FOXP3+ T regulatory cells in human autoimmunity:more than a numbers game[J].J Immunol,2011,187(5):2061-2066.
[5] Sakaguchi S,Sakaguchi N,Asano M,et al.Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25).Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J].J Immunol,1995,155(3):1151-1164.
[6] Kitagawa Y,Sakaguchi S.Molecular control of regulatory T cell development and function[J].Curr Opin Immunol,2017,49:64-70.
[7] Hori S,Nomura T,Sakaguchi S.Control of regulatory T cell development by the transcription factor Foxp3[J].Science,2003,299(5609):1057-1061.
[8] Marson A,Kretschmer K,Frampton G M,et al.Foxp3 occupancy and regulation of key target genes during T-cell stimulation[J].Nature,2007,445(7130):931-935.
[9] Pinheiro D,Singh Y,Grant C R,et al.Phenotypic and functional characterization of a CD4(+) CD25(high) FOXP3(high) regulatory T-cell population in the dog[J].Immunology,2011,132(1):111-122.
[10] Zhang H,Kong H,Zeng X,et al.Subsets of regulatory T cells and their roles in allergy[J].J Transl Med,2014,12:125.
[11] Bocian K,Kiernozek E,Domagala-Kulawik J,et al.Expanding diversity and common goal of regulatory T and B Cells.I:origin,phenotype,mechanisms[J].Arch Immunol Ther Exp (Warsz),2017,65(6):501-520.
[12] Kosten I J,Rustemeyer T.Generation,subsets and functions of inducible regulatory T cells[J].Antiinflamm Antiallergy Agents Med Chem,2015,13(3):139-53.
[13] Zhu Z F,Meng K,Zhong Y C,et al.Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study[J].PLoS One,2014,9(2):e88775.
[14] Dietel B,Cicha I,Voskens C J,et al.Decreased numbers of regulatory T cells are associated with human atherosclerotic lesion vulnerability and inversely correlate with infiltrated mature dendritic cells[J].Atherosclerosis,2013,230(1):92-99.
[15] Jia L,Zhu L,Wang J Z,et al.Methylation of FOXP3 in regulatory T cells is related to the severity of coronary artery disease[J].Atherosclerosis,2013,228(2):346-352.
[16] George J,Schwartzenberg S,Medvedovsky D,et al.Regulatory T cells and IL-10 levels are reduced in patients with vulnerable coronary plaques[J].Atherosclerosis,2012,222(2):519-523.
[17] Wigren M,Bjorkbacka H,Andersson L,et al.Low levels of circulating CD4+FoxP3+ T cells are associated with an increased risk for development of myocardial infarction but not for stroke[J].Arterioscler Thromb Vasc Biol,2012,32(8):2000-2004.
[18] Butcher M J,Filipowicz A R,Waseem T C,et al.Atherosclerosis-driven treg plasticity results in formation of a dysfunctional subset of plastic IFNgamma+ Th1/Tregs[J].Circ Res,2016,119(11):1190-1203.
[19] Liu Z D,Wang L,Lu F H,et al.Increased Th17 cell frequency concomitant with decreased Foxp3+ Treg cell frequency in the peripheral circulation of patients with carotid artery plaques[J].Inflamm Res,2012,61(10):1155-1165.
[20] Dai X,Zhang D,Wang C,et al.The pivotal role of thymus in atherosclerosis mediated by immune and inflammatory response[J].Int J Med Sci,2018,15(13):1555-1563.
[21] Xue-Mei L,Jie C,Xuan D,et al.Changes in CD4(+)CD25(+) Tregs in the pathogenesis of atherosclerosis in ApoE(-/-) mice[J].Exp Biol Med (Maywood),2017,242(9):918-925.
[22] Li M O,Flavell R A.TGF-beta:a master of all T cell trades[J].Cell,2008,134(3):392-404.
[23] Toma I,Mccaffrey T A.Transforming growth factor-beta and atherosclerosis:interwoven atherogenic and atheroprotective aspects[J].Cell Tissue Res,2012,347(1):155-175.
[24] Krishna S M,Seto S W,Jose R J,et al.A peptide antagonist of thrombospondin-1 promotes abdominal aortic aneurysm progression in the angiotensin II-infused apolipoprotein-E-deficient mouse[J].Arterioscler Thromb Vasc Biol,2015,35(2):389-398.
[25] Bobryshev Y V,Sobenin I A,Orekhov A N,et al.Novel anti-inflammatory interleukin-35 as an emerging target for antiatherosclerotic therapy[J].Curr Pharm Des,2015,21(9):1147-1151.
[26] Collison L W,Workman C J,Kuo T T,et al.The inhibitory cytokine IL-35 contributes to regulatory T-cell function[J].Nature,2007,450(7169):566-569.
[27] 郭亚妮,毛艳阳,刘娜娜,等.中性粒细胞/淋巴细胞与急性冠状动脉综合征相关性的研究进展[J].心肺血管病杂志,2017,36(4):322-323,326.
[28] Peled M,Fisher E A.Dynamic aspects of macrophage polarization during atherosclerosis progression and regression[J].Front Immunol,2014,5:579.
[29] Lin J,Li M,Wang Z,et al.The role of CD4+CD25+ regulatory T cells in macrophage-derived foam-cell formation[J].J Lipid Res,2010,51(5):1208-1217.
[30] Ou H X,Guo B B,Liu Q,et al.Regulatory T cells as a new therapeutic target for atherosclerosis[J].Acta Pharmacol Sin,2018.
[31] 尼菲拉·甫拉提,穆叶赛·尼加提.急性冠状动脉综合征相关新生物标志物研究现状[J].心肺血管病杂志,2017,36(2):137-139.
[32] Meng X,Li W,Yang J,et al.Regulatory T cells prevent plaque disruption in apolipoprotein E-knockout mice[J].Int J Cardiol,2013,168(3):2684-2692.
[33] Hu Y W,Wang Q,Ma X,et al.TGF-beta1 up-regulates expression of ABCA1,ABCG1 and SR-BI through liver X receptor alpha signaling pathway in THP-1 macrophage-derived foam cells[J].J Atheroscler Thromb,2010,17(5):493-502.
[34] Subramanian M,Thorp E,Hansson G K,et al.Treg-mediated suppression of atherosclerosis requires MYD88 signaling in DCs[J].J Clin Invest,2013,123(1):179-188.
[35] Foks A C,Frodermann V,Ter Borg M,et al.Differential effects of regulatory T cells on the initiation and regression of atherosclerosis[J].Atherosclerosis,2011,218(1):53-60.
[36] Haddad Y,Lahoute C,Clement M,et al.The dendritic cell receptor DNGR-1 promotes the development of atherosclerosis in mice[J].Circ Res,2017,121(3):234-243.
[37] Shen X,Niu C,Konig R.Increased numbers and suppressive activity of regulatory CD25(+)CD4(+) T lymphocytes in the absence of CD4 engagement by MHC class II molecules[J].Cell Immunol,2013,282(2):117-128.
[38] Gu P,Gao J F,D'souza C A,et al.Trogocytosis of CD80 and CD86 by induced regulatory T cells[J].Cell Mol Immunol,2012,9(2):136-146.
[39] Chattopadhyay G,Shevach E M.Antigen-specific induced T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism[J].J Immunol,2013,191(12):5875-5884.
[40] Ait-Oufella H,Herbin O,Bouaziz J D,et al.B cell depletion reduces the development of atherosclerosis in mice[J].J Exp Med,2010,207(8):1579-1587.
[41] Wang P,Zheng S G.Regulatory T cells and B cells:implication on autoimmune diseases[J].Int J Clin Exp Pathol,2013,6(12):2668-2674.
[42] Spitz C,Winkels H,Burger C,et al.Regulatory T cells in atherosclerosis:critical immune regulatory function and therapeutic potential[J].Cell Mol Life Sci,2016,73(5):901-922.
[43] Tselios K,Sarantopoulos A,Gkougkourelas I,et al.T regulatory cells:a promising new target in atherosclerosis[J].Crit Rev Immunol,2014,34(5):389-397.
[2] Sasaki N,Yamashita T,Takeda M,et al.Regulatory T cells in atherogenesis[J].J Atheroscler Thromb,2012,19(6):503-15.
[3] Hansson G K.Inflammation,atherosclerosis,and coronary artery disease[J].N Engl J Med,2005,352(16):1685-95.
[4] Long S A,Buckner J H.CD4+FOXP3+ T regulatory cells in human autoimmunity:more than a numbers game[J].J Immunol,2011,187(5):2061-2066.
[5] Sakaguchi S,Sakaguchi N,Asano M,et al.Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25).Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J].J Immunol,1995,155(3):1151-1164.
[6] Kitagawa Y,Sakaguchi S.Molecular control of regulatory T cell development and function[J].Curr Opin Immunol,2017,49:64-70.
[7] Hori S,Nomura T,Sakaguchi S.Control of regulatory T cell development by the transcription factor Foxp3[J].Science,2003,299(5609):1057-1061.
[8] Marson A,Kretschmer K,Frampton G M,et al.Foxp3 occupancy and regulation of key target genes during T-cell stimulation[J].Nature,2007,445(7130):931-935.
[9] Pinheiro D,Singh Y,Grant C R,et al.Phenotypic and functional characterization of a CD4(+) CD25(high) FOXP3(high) regulatory T-cell population in the dog[J].Immunology,2011,132(1):111-122.
[10] Zhang H,Kong H,Zeng X,et al.Subsets of regulatory T cells and their roles in allergy[J].J Transl Med,2014,12:125.
[11] Bocian K,Kiernozek E,Domagala-Kulawik J,et al.Expanding diversity and common goal of regulatory T and B Cells.I:origin,phenotype,mechanisms[J].Arch Immunol Ther Exp (Warsz),2017,65(6):501-520.
[12] Kosten I J,Rustemeyer T.Generation,subsets and functions of inducible regulatory T cells[J].Antiinflamm Antiallergy Agents Med Chem,2015,13(3):139-53.
[13] Zhu Z F,Meng K,Zhong Y C,et al.Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study[J].PLoS One,2014,9(2):e88775.
[14] Dietel B,Cicha I,Voskens C J,et al.Decreased numbers of regulatory T cells are associated with human atherosclerotic lesion vulnerability and inversely correlate with infiltrated mature dendritic cells[J].Atherosclerosis,2013,230(1):92-99.
[15] Jia L,Zhu L,Wang J Z,et al.Methylation of FOXP3 in regulatory T cells is related to the severity of coronary artery disease[J].Atherosclerosis,2013,228(2):346-352.
[16] George J,Schwartzenberg S,Medvedovsky D,et al.Regulatory T cells and IL-10 levels are reduced in patients with vulnerable coronary plaques[J].Atherosclerosis,2012,222(2):519-523.
[17] Wigren M,Bjorkbacka H,Andersson L,et al.Low levels of circulating CD4+FoxP3+ T cells are associated with an increased risk for development of myocardial infarction but not for stroke[J].Arterioscler Thromb Vasc Biol,2012,32(8):2000-2004.
[18] Butcher M J,Filipowicz A R,Waseem T C,et al.Atherosclerosis-driven treg plasticity results in formation of a dysfunctional subset of plastic IFNgamma+ Th1/Tregs[J].Circ Res,2016,119(11):1190-1203.
[19] Liu Z D,Wang L,Lu F H,et al.Increased Th17 cell frequency concomitant with decreased Foxp3+ Treg cell frequency in the peripheral circulation of patients with carotid artery plaques[J].Inflamm Res,2012,61(10):1155-1165.
[20] Dai X,Zhang D,Wang C,et al.The pivotal role of thymus in atherosclerosis mediated by immune and inflammatory response[J].Int J Med Sci,2018,15(13):1555-1563.
[21] Xue-Mei L,Jie C,Xuan D,et al.Changes in CD4(+)CD25(+) Tregs in the pathogenesis of atherosclerosis in ApoE(-/-) mice[J].Exp Biol Med (Maywood),2017,242(9):918-925.
[22] Li M O,Flavell R A.TGF-beta:a master of all T cell trades[J].Cell,2008,134(3):392-404.
[23] Toma I,Mccaffrey T A.Transforming growth factor-beta and atherosclerosis:interwoven atherogenic and atheroprotective aspects[J].Cell Tissue Res,2012,347(1):155-175.
[24] Krishna S M,Seto S W,Jose R J,et al.A peptide antagonist of thrombospondin-1 promotes abdominal aortic aneurysm progression in the angiotensin II-infused apolipoprotein-E-deficient mouse[J].Arterioscler Thromb Vasc Biol,2015,35(2):389-398.
[25] Bobryshev Y V,Sobenin I A,Orekhov A N,et al.Novel anti-inflammatory interleukin-35 as an emerging target for antiatherosclerotic therapy[J].Curr Pharm Des,2015,21(9):1147-1151.
[26] Collison L W,Workman C J,Kuo T T,et al.The inhibitory cytokine IL-35 contributes to regulatory T-cell function[J].Nature,2007,450(7169):566-569.
[27] 郭亚妮,毛艳阳,刘娜娜,等.中性粒细胞/淋巴细胞与急性冠状动脉综合征相关性的研究进展[J].心肺血管病杂志,2017,36(4):322-323,326.
[28] Peled M,Fisher E A.Dynamic aspects of macrophage polarization during atherosclerosis progression and regression[J].Front Immunol,2014,5:579.
[29] Lin J,Li M,Wang Z,et al.The role of CD4+CD25+ regulatory T cells in macrophage-derived foam-cell formation[J].J Lipid Res,2010,51(5):1208-1217.
[30] Ou H X,Guo B B,Liu Q,et al.Regulatory T cells as a new therapeutic target for atherosclerosis[J].Acta Pharmacol Sin,2018.
[31] 尼菲拉·甫拉提,穆叶赛·尼加提.急性冠状动脉综合征相关新生物标志物研究现状[J].心肺血管病杂志,2017,36(2):137-139.
[32] Meng X,Li W,Yang J,et al.Regulatory T cells prevent plaque disruption in apolipoprotein E-knockout mice[J].Int J Cardiol,2013,168(3):2684-2692.
[33] Hu Y W,Wang Q,Ma X,et al.TGF-beta1 up-regulates expression of ABCA1,ABCG1 and SR-BI through liver X receptor alpha signaling pathway in THP-1 macrophage-derived foam cells[J].J Atheroscler Thromb,2010,17(5):493-502.
[34] Subramanian M,Thorp E,Hansson G K,et al.Treg-mediated suppression of atherosclerosis requires MYD88 signaling in DCs[J].J Clin Invest,2013,123(1):179-188.
[35] Foks A C,Frodermann V,Ter Borg M,et al.Differential effects of regulatory T cells on the initiation and regression of atherosclerosis[J].Atherosclerosis,2011,218(1):53-60.
[36] Haddad Y,Lahoute C,Clement M,et al.The dendritic cell receptor DNGR-1 promotes the development of atherosclerosis in mice[J].Circ Res,2017,121(3):234-243.
[37] Shen X,Niu C,Konig R.Increased numbers and suppressive activity of regulatory CD25(+)CD4(+) T lymphocytes in the absence of CD4 engagement by MHC class II molecules[J].Cell Immunol,2013,282(2):117-128.
[38] Gu P,Gao J F,D'souza C A,et al.Trogocytosis of CD80 and CD86 by induced regulatory T cells[J].Cell Mol Immunol,2012,9(2):136-146.
[39] Chattopadhyay G,Shevach E M.Antigen-specific induced T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism[J].J Immunol,2013,191(12):5875-5884.
[40] Ait-Oufella H,Herbin O,Bouaziz J D,et al.B cell depletion reduces the development of atherosclerosis in mice[J].J Exp Med,2010,207(8):1579-1587.
[41] Wang P,Zheng S G.Regulatory T cells and B cells:implication on autoimmune diseases[J].Int J Clin Exp Pathol,2013,6(12):2668-2674.
[42] Spitz C,Winkels H,Burger C,et al.Regulatory T cells in atherosclerosis:critical immune regulatory function and therapeutic potential[J].Cell Mol Life Sci,2016,73(5):901-922.
[43] Tselios K,Sarantopoulos A,Gkougkourelas I,et al.T regulatory cells:a promising new target in atherosclerosis[J].Crit Rev Immunol,2014,34(5):389-397.