Th17/Treg细胞在脑卒中后抑郁发病机制中的研究进展
摘要
<正>脑卒中后抑郁涉及到一系列复杂的机制,免疫功能紊乱在脑卒中后抑郁的病理生理过程中可能发挥重要作用,尤其是Th17/Treg细胞及其相关细胞因子的失衡,通过影响神经递质的合成及代谢,引起其功能下降,最终导致抑郁的发生。本研究就Th17/Treg细胞及其相关细胞因子与脑卒中后抑郁的关系作一综述。脑卒中后抑郁( post-stroke depression,PSD)是一种以情感低沉、兴趣下降、睡眠障碍、疲乏甚至出现自杀企图等为主要表现的情感
引文
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[26] Aulin J,Siegbahn A,Hijazi Z,et al.Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation[J].American Heart Journal,2015,170(6):1151-1160.
[27] Esenwa CC,Elkind MS.Inflammatory risk factors,biomarkers and associated therapy in ischaemic stroke[J].Nature Reviews Neurology,2016,12(10):594-604.
[28] Fr YSHOV HM,Bj Rnerem,Engstad T,et al.Elevated inflammatory markers predict mortality in long-term ischemic stroke-survivors:a population-based prospective study[J].Aging Clinical and Experimental Research,2017,29(3):379-385.
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[31] Benakis C,Brea D,Caballero S,et al.Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells[J].Nature Medicine,2016,22(5):516-523.
[32] Abbas A,Gregersen I,Holm S,et al.Interleukin 23 levels are increased in carotid atherosclerosis possible role for the interleukin 23/interleukin 17 axis[J].Stroke,2015,46(3):793.
[33] Zheng Y,Zhong D,Chen H,et al.Pivotal role of cerebral interleukin-23 during immunologic injury in delayed cerebral ischemia in mice[J].Neuroscience,2015,290:321-331.
[34] Zhao HR,Wan LH,Chen Y,et al.FasL incapacitation alleviates CD4(+) T cells-induced brain injury through remodeling of microglia polarization in mouse ischemic stroke[J].Journal of Neuroimmunology,2018,318:36-44.
[35] Li Q,Wang YP,Yu F,et al.Peripheral Th17/Treg imbalance in patients with atherosclerotic cerebral infarction[J].International Journal of Clinical and Experimental Pathology,2013,6(6):1015-1027.
[36] Dolati S,Ahmadi M,Khalili M,et al.Peripheral Th17/Treg imbalance in elderly patients with ischemic stroke[J].Neurological Sciences,2018,39(4):647-654.
[37] Hu YH,Zheng YH,Wu Y,et al.Imbalance between IL-17A-Producing Cells and Regulatory T Cells during Ischemic Stroke[J].Mediators of Inflammation,2014(2):813045.
[38] Liu CS,Adibfar A,Herrmann N,et al.Evidence for Inflammation-Associated Depression[J].Curr Top Behav Neurosci,2016,31:3-30.
[39] Müller N,Myint AM,Schwarz MJ.Inflammatory Biomarkers And Depression[J].Neurotoxicity Research,2011,19(2):308-318.
[40] Alshogran OY,Khalil AA,Oweis AO,et al.Association of brain-derived neurotrophic factor and interleukin-6 serum levels with depressive and anxiety symptoms in hemodialysis patients[J].GENERAL HOSPITAL PSYCHIATRY,2018,53:25-31.
[41] Davami MH,Baharlou R,Ahmadi VA,et al.Elevated IL-17 and TGF-β serum levels:a positive correlation between t-helper 17 Cell-Related Pro-Inflammatory responses with major depressive disorder[J].Basic Clin Neurosci,2016,7(2):137-142.
[42] Hong M,Zheng J,Ding ZY,et al.Imbalance between Th17 and Treg Cells May Play an Important Role in the Development of Chronic Unpredictable Mild Stress-Induced Depression in Mice[J].Neuroimmunomodulation,2013,20(1):39-50.
[43] Beurel E,Harrington LE,Jope R S.Inflammatory Th17 cells promote depression-like behavior in mice[J].Biological Psychiatry,2013,73(7):622.
[44] Beurel E,Lowell JA.Th17 cells in depression[J].Brain Behavior and Immunity,2018,69:28-34.
[45] Su Jian-an,Chou SY,Tsai CS,et al.Cytokine changes in the pathophysiology of poststroke depression[J].General Hospital Psychiatry,2012,34(1):35-39.
[46] Jiao JT,Cheng C,Ma YJ,et al.Association between inflammatory cytokines and the risk of post-stroke depression,and the effect of depression on outcomes of patients with ischemic stroke in a 2-year prospective study[J].Experimental and Therapeutic Medicine,2016,12(3):1591-1598.
[47] Mu YY,Wang Z,Zhou J,et al.Correlations of post-stroke depression with inflammatory response factors[J].Iranian Journal of Public Health,2018,47(7):988-993.
[48] Kim JM,Stewart R,Kim SW,et al.Associations of cytokine gene polymorphisms with post-stroke depression[J].World Journal of Biological Psychiatry,2012,13(8):579-587.
[49] Yasuno F,Taguchi A,Yamamoto A,et al.Microstructural abnormality in white matter,regulatory T lymphocytes,and depressive symptoms after stroke[J].Psychogeriatrics:the Official Journal of the Japanese Psychogeriatric Society,2014,14(4):213-221.
[2] Gaffen SL,Jain R,Garg AV,et al.The IL-23-IL-17 immune axis:from mechanisms to therapeutic testing[J].Nature Reviews Immunology,2014,14(9):585-600.
[3] Ivanov II,Mckenzie BS,Zhou L,et al.The orphan nuclear receptor ROR gamma t directs the differentiation program of proinflammatory IL-17(+) T helper cells[J].Cell,2006,126(6):1121-1133.
[4] Unutmaz D.Rorc2:the master of human Th17 cell programming[J].European Journal of Immunology,2009,39(6):1452-1455.
[5] Veldhoen M,Hocking RJ,Atkins CJ,et al.TGFβ in the context of an inflammatory cytokine milieu supports De Novo differentiation of IL-17-Producing T cells[J].Immunity,2006,24(2):179-189.
[6] Bettelli E,Carrier Y,Gao Wenda,et al.Reciprocal developmental pathways for the Generation of pathogenic effector TH17 and regulatory T cells[J].Nature,2006,441(790):235-238.
[7] Zhang S,Takaku M,Zou LY,et al.Reversing SKI-SMAD4-mediated suppression is essential for T(H)17 cell differentiation[J].Nature,2017,551(7678):105.
[8] Zhou L,Ivanov II,Spolski R,et al.IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways[J].Nature Immunology,2007,8(9):967-974.
[9] Chung Y,Chang SH,Martinez GJ,et al.Critical regulation of early Th17 cell differentiation by IL-1 signaling[J].Journal of Immunology,2009,182(1):576-587.
[10] Mcgeachy MJ,Bak-Jensen KS,Chen Y,et al.TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology[J].Nature Immunology,2007,8(12):1390-1397.
[11] Lee YJ,Awasthi A,Yosef N,et al.Induction and molecular signature of pathogenic TH17 cells[J].Nature Immunology,2012,13(10):991-999.
[12] Toker A,Engelbert D,Garg G,et al.Active demethylation of the Foxp3 locus leads to the Generation of stable regulatory T cells within the thymus[J].Journal of Immunology,2013,190(7):3180-3188.
[13] Brunkow ME,Jeffery EW,Hjerrild KA,et al.Disruption of a new forkhead/winged-helix protein,scurfin,results in the fatal lymphoproliferative disorder of the scurfy mouse[J].Nature Genetics,2001,27(1):68-73.
[14] Ghosh S,Roy-Chowdhuris R,Kang K,et al.The transcription factor Foxp1 preserves integrity of an active Foxp3 locus in extrathymic Tregcells[J].Nat Commun2018 Oct 26,9(1):4473.
[15] Wu C,Chen ZJ,Dardalhon V,et al.The transcription factor musculin promotes the unidirectional development of peripheral T-reg cells by suppressing the T(H)2 transcriptional program[J].Nature Immunology,2017,18(3):344-353.
[16] Lee W,Kim HS,Hwang SS,et al.The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery[J].Experimental and Molecular Medicine,2017,49(11):e393.
[17] Goldstein JD,Perol L,Zaragoza BA,et al.Role of cytokines in tymus- versus peripherally derived-regulatory T cell differentiation and function[J].Frontiers in Immunology,2013,4:155.
[18] Li XD,Liang YQ,Leblanc M,et al.Function of a Foxp3 cis-Element in protecting regulatory T cell identity[J].Cell,2014,158(4):734-748.
[19] Nair VS,Oh KI.Down-regulation of Tet2 prevents TSDR demethylation in IL2 deficient regulatory T cells[J].Biochemical and Biophysical Research Communications,2014,450(1):918-924.
[20] Yang RL,Qu CY,Zhou Y,et al.Hydrogen sulfide promotes Tet1-and Tet2-Mediated Foxp3 demethylation to drive regulatory T cell differentiation and maintain immune homeostasis[J].Immunity,2015,43(2):251-263.
[21] Zhang DF,Chia C,Jiao Xu-e,et al.D-mannose induces regulatory T cells and suppresses immunopathology[J].Nature Medicine,2017,23(9):1036.
[22] Zhou L,Lopes JE,Chong MM,et al.TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function[J].Nature,2008,453(7192):236-240.
[23] Mucida D,Park Y,Kim G,et al.Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid[J].Science (New York,N.Y.),2007,317(5835):256-260.
[24] Elali A,Leblanc NJ.The role of monocytes in ischemic stroke pathobiology:new avenues to explore[J].Frontiers in Aging Neuroscience,2016,8(29):29.
[25] Rothenburg LS,Herrmann N,Swardfager W A,et al.The relationship between inflammatory markers and post stroke cognitive impairment[J].Journal of Geriatric Psychiatry and Neurology,2010,23(3):199-205.
[26] Aulin J,Siegbahn A,Hijazi Z,et al.Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation[J].American Heart Journal,2015,170(6):1151-1160.
[27] Esenwa CC,Elkind MS.Inflammatory risk factors,biomarkers and associated therapy in ischaemic stroke[J].Nature Reviews Neurology,2016,12(10):594-604.
[28] Fr YSHOV HM,Bj Rnerem,Engstad T,et al.Elevated inflammatory markers predict mortality in long-term ischemic stroke-survivors:a population-based prospective study[J].Aging Clinical and Experimental Research,2017,29(3):379-385.
[29] Boehme AK,Mcclure LA,Zhang Y,et al.Inflammatory markers and outcomes after lacunar stroke levels of inflammatory markers in treatment of stroke study[J].Stroke;a Journal of Cerebral Circulation,2016,47(3):659-667.
[30] Zuo L,Shi LH,Yan FL.The reciprocal interaction of sympathetic nervous system and cAMP-PKA-NF-kB pathway in immune suppression after experimental stroke[J].Neuroscience Letters,2016,627:205-210.
[31] Benakis C,Brea D,Caballero S,et al.Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells[J].Nature Medicine,2016,22(5):516-523.
[32] Abbas A,Gregersen I,Holm S,et al.Interleukin 23 levels are increased in carotid atherosclerosis possible role for the interleukin 23/interleukin 17 axis[J].Stroke,2015,46(3):793.
[33] Zheng Y,Zhong D,Chen H,et al.Pivotal role of cerebral interleukin-23 during immunologic injury in delayed cerebral ischemia in mice[J].Neuroscience,2015,290:321-331.
[34] Zhao HR,Wan LH,Chen Y,et al.FasL incapacitation alleviates CD4(+) T cells-induced brain injury through remodeling of microglia polarization in mouse ischemic stroke[J].Journal of Neuroimmunology,2018,318:36-44.
[35] Li Q,Wang YP,Yu F,et al.Peripheral Th17/Treg imbalance in patients with atherosclerotic cerebral infarction[J].International Journal of Clinical and Experimental Pathology,2013,6(6):1015-1027.
[36] Dolati S,Ahmadi M,Khalili M,et al.Peripheral Th17/Treg imbalance in elderly patients with ischemic stroke[J].Neurological Sciences,2018,39(4):647-654.
[37] Hu YH,Zheng YH,Wu Y,et al.Imbalance between IL-17A-Producing Cells and Regulatory T Cells during Ischemic Stroke[J].Mediators of Inflammation,2014(2):813045.
[38] Liu CS,Adibfar A,Herrmann N,et al.Evidence for Inflammation-Associated Depression[J].Curr Top Behav Neurosci,2016,31:3-30.
[39] Müller N,Myint AM,Schwarz MJ.Inflammatory Biomarkers And Depression[J].Neurotoxicity Research,2011,19(2):308-318.
[40] Alshogran OY,Khalil AA,Oweis AO,et al.Association of brain-derived neurotrophic factor and interleukin-6 serum levels with depressive and anxiety symptoms in hemodialysis patients[J].GENERAL HOSPITAL PSYCHIATRY,2018,53:25-31.
[41] Davami MH,Baharlou R,Ahmadi VA,et al.Elevated IL-17 and TGF-β serum levels:a positive correlation between t-helper 17 Cell-Related Pro-Inflammatory responses with major depressive disorder[J].Basic Clin Neurosci,2016,7(2):137-142.
[42] Hong M,Zheng J,Ding ZY,et al.Imbalance between Th17 and Treg Cells May Play an Important Role in the Development of Chronic Unpredictable Mild Stress-Induced Depression in Mice[J].Neuroimmunomodulation,2013,20(1):39-50.
[43] Beurel E,Harrington LE,Jope R S.Inflammatory Th17 cells promote depression-like behavior in mice[J].Biological Psychiatry,2013,73(7):622.
[44] Beurel E,Lowell JA.Th17 cells in depression[J].Brain Behavior and Immunity,2018,69:28-34.
[45] Su Jian-an,Chou SY,Tsai CS,et al.Cytokine changes in the pathophysiology of poststroke depression[J].General Hospital Psychiatry,2012,34(1):35-39.
[46] Jiao JT,Cheng C,Ma YJ,et al.Association between inflammatory cytokines and the risk of post-stroke depression,and the effect of depression on outcomes of patients with ischemic stroke in a 2-year prospective study[J].Experimental and Therapeutic Medicine,2016,12(3):1591-1598.
[47] Mu YY,Wang Z,Zhou J,et al.Correlations of post-stroke depression with inflammatory response factors[J].Iranian Journal of Public Health,2018,47(7):988-993.
[48] Kim JM,Stewart R,Kim SW,et al.Associations of cytokine gene polymorphisms with post-stroke depression[J].World Journal of Biological Psychiatry,2012,13(8):579-587.
[49] Yasuno F,Taguchi A,Yamamoto A,et al.Microstructural abnormality in white matter,regulatory T lymphocytes,and depressive symptoms after stroke[J].Psychogeriatrics:the Official Journal of the Japanese Psychogeriatric Society,2014,14(4):213-221.