干扰素调节因子8(IRF8)在髓系细胞形成和相关疾病中的作用
摘要
干扰素调节因子8(IRF8)是造血细胞中表达的转录因子,调控一系列转录因子的功能和表观遗传改变。在单核吞噬细胞祖细胞中,IRF8与富含嘌呤盒1(PU.1)联合促进末端增强子的形成,诱导单核细胞相关基因包括关键的下游Krüppel样因子4(KLF4)的表达,调节单核细胞的形成;IRF8还可以促进树突状细胞、嗜酸粒细胞和嗜碱粒细胞的形成;IRF8通过抑制CCAAT增强子结合蛋白α(C/EBPα)的活性来抑制中性粒细胞的分化程序从而抑制中性粒细胞的产生。IRF8-/-单核吞噬细胞祖细胞不能分化成单核细胞、吞噬细胞,反而异常引起中性粒细胞产生。IRF8-/-小鼠及IRF8表达缺失或突变的人都会表现出免疫缺陷和类慢性粒细胞性疾病。本文主要概括IRF8在髓系细胞形成及在相关疾病中重要作用。
引文
[1]Tamura T,Kurotaki D,Koizumi S I.Regulation of myelopoiesis by the transcription factor IRF8[J].Int J Hematol,2015,101(4):342-351.
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[5]Hettinger J,Richards D M,Hansson J,et al.Origin of monocytes and macrophages in a committed progenitor[J].Nat Immunol,2013,14(8):821-830.
[6]Saito Y,Ellegast J M,Manz M G.Generation of humanized mice for analysis of human dendritic cells[J].Methods Mol Biol,2016,1423:309-320.
[7]Chopin M,Seillet C,Chevrier S,et al.Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks[J].J Exp Med,2013,210(13):2967-2980.
[8]Sasaki H,Kurotaki D,Osato N,et al.Transcription factor IRF8plays a critical role in the development of murine basophils and mast cells[J].Blood,2015,125(2):358-369.
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[16]Lee W,Kim H S,Baek S Y,et al.Transcription factor IRF8controls Th1-like regulatory T-cell function[J/OL].Cell Mol Immunol,2016,13(6):785-794.
[17]Salem S,Langlais D,Lefebvre F,et al.Functional characterization of the human dendritic cell immunodeficiency associated with the IRF8(K108E)mutation[J].Blood,2014,124(12):1894-1904.
[18]Liu X,Ren S,Ge C,et al.Sca-1+Lin-CD117-mesenchymal stem/stromal cells induce the generation of novel IRF8-controlled regulatory dendritic cells through Notch-RBP-J signaling[J].J Immunol,2015,194(9):4298-4308.
[19]Murphy T L,Tussiwand R,Murphy K M.Specificity through cooperation:BATF-IRF interactions control immune-regulatory networks[J]Nat Rev Immunol,2013,13(7):499-509.
[20]Garjales-Reyes G E,Iwata A,Albring J,et al.Batf3 maintains autoactivation of Irf8 for commitment of a CD8α+conventional DC clonogenic progenitor[J].Nat Immunol,2015,16(7):708-717.
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[24]ChauvistréH,Küstermann C,Rehage N,et al.Dendritic cell development requires histone deacetylase activity[J].Eur J Immunol,2014,44(8):2478-2488.
[25]Singh H,Glasmacher E,Chang A B,et al.The molecular choreography of IRF4 and IRF8 with immune system partners[J].Cold Spring Harb Symp Quant Biol,2013,78:101-104.
[26]Paschall A V,Zhang R,Qi C F,et al.IFN regulatory factor 8 represses GM-CSF expression in T cells to affect myeloid cell lineage differentiation[J].J Immunol,2015,194(5):2369-2379.
[27]Yáez A,Ng M Y,Hassanzadeh-Kiabi N,et al.IRF8 acts in lineagecommitted rather than oligopotent progenitors to control neutrophil vsmonocyte production[J/OL].Blood,2015,125(9):1452-1459.
[28]Waight J D,Netherby C,Hensen M L,et al.Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis[J/OL].J Clin Invest,2013,123(10):4464-4478.
[29]Bhattacharya D.Basophils take a slice of IRF8 pie[J].Blood,2015,125(2):214-215.
[30]Scheller M,Schnheit J,Zimmermann K,et al.Cross talk between Wnt/β-catenin and Irf8 in leukemia progression and drug resistance[J].J Exp Med,2013,210(11):2239-2256.
[31]Hu L,Huang W,Hjort E E,et al.The interferon consensus sequence binding protein(Icsbp/Irf8)is required for termination of emergency granulopoiesis[J].J Bio Chem,2016,291(8):4107-4120.
[32]Watanabe T,Hotta C,Koizumi S,et al.The transcription factor IRF8 counteracts BCR-ABL to rescue dendritic cell development in chronic myelogenous leukemia[J].Cancer Res,2013,73(22):6642-6653.
[33]Waight J D,Banik D,Griffiths E A,et al.Regulation of the interferon regulatory factor-8(IRF-8)tumor suppressor gene by the signal transducer and activator of transcription 5(STAT5)transcription factor in chronic myeloid leukemia[J].J Biol Chem,2014,289(22):15642-15652.
[34]Vander Lugt B,Khan A A,Hackney J A,et al.Transcriptional programming of dendritic cells for enhanced MHC classⅡantigen presentation[J].Nat Immunol,2014,15(2):161-167.
[35]Lin J D,Wang Y H,Liu C H,et al.Association of IRF8 gene polymorphisms with autoimmune thyroid disease[J].Eur J Clini Invest,2015,45(7):711-719.
[36]Zhang Q,Zhang L,Li L,et al.Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis[J].Cancer Lett,2014,354(2):227-234.
[2]Vogelsang P,Karlsen M,Brun J G,et al.Altered phenotype and Stat1 expression in Toll-like receptor 7/8 stimulated monocytederived dendritic cells from patients with primary Sjgren’s syndrome[J/OL].Arthritis Res Ther,2014,16(4):R166.doi:10.1186/ar4682.
[3]Kurotaki D,Yamamoto M,Nishiyama A,et al.IRF8 inhibits C/EBPαactivity to restrain mononuclear phagocyte progenitors from differentiating into neutrophils[J/OL].Nat Commun,2014,5:4978.doi:10.1038/ncomms5978.
[4]Wang H,Yan M,Sun J,et al.A reporter mouse reveals lineagespecific and heterogeneous expression of IRF8 during lymphoid and myeloid cell differentiation[J].J Immunol,2014,193(4):1766-1777.
[5]Hettinger J,Richards D M,Hansson J,et al.Origin of monocytes and macrophages in a committed progenitor[J].Nat Immunol,2013,14(8):821-830.
[6]Saito Y,Ellegast J M,Manz M G.Generation of humanized mice for analysis of human dendritic cells[J].Methods Mol Biol,2016,1423:309-320.
[7]Chopin M,Seillet C,Chevrier S,et al.Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks[J].J Exp Med,2013,210(13):2967-2980.
[8]Sasaki H,Kurotaki D,Osato N,et al.Transcription factor IRF8plays a critical role in the development of murine basophils and mast cells[J].Blood,2015,125(2):358-369.
[9]Yáez A,Goodridge H S.Interferon regulatory factor 8 and the regulation of neutrophil,monocyte,and dendritic cell production[J].Curr Opin Hematol,2016,23(1):11-17.
[10]Zhao Y,Wu T,Shao S,et al.Phenotype,development,and biological function of myeloid-derived suppressor cells[J/OL].Oncoimmunology,2015,5(2):e1004983.e Collection 2016.
[11]Mancino A,Termanini A,Barozzi I,et al.A dual cis-regulatory code links IRF8 to constitutive and inducible gene expression in macrophages[J].Genes Dev,2015,29(4):394-408.
[12]Guilliams M,Ginhoux F,Jakubzick C,et al.Dendritic cells,monocytes and macrophages:a unified nomenclature based on ontogeny[J].Nat Rev Immunol,2014,14(8):571-578.
[13]Gupta M,Shin D M,Ramakrishna L,et al.IRF8 directs stressinduced autophagy in macrophages and promotes clearance of Listeria monocytogenes[J/OL].Nat Commun,2015,6:6379.doi:10.1038/ncomms7379.
[14]Shim K S,Ha H,Kim T,et al.Orostachys japonicus suppresses osteoclast differentiation by inhibiting NFATc1 expression[J].Am J Chin Med,2015,43(5):1013-1030.
[15]Cohen S B,Smith N L,Mcdougal C,et al.Beta-catenin signaling drives differentiation and proinflammatory function of IRF8-dependent dendritic cells[J].J Immunol,2015,194(1):210-222.
[16]Lee W,Kim H S,Baek S Y,et al.Transcription factor IRF8controls Th1-like regulatory T-cell function[J/OL].Cell Mol Immunol,2016,13(6):785-794.
[17]Salem S,Langlais D,Lefebvre F,et al.Functional characterization of the human dendritic cell immunodeficiency associated with the IRF8(K108E)mutation[J].Blood,2014,124(12):1894-1904.
[18]Liu X,Ren S,Ge C,et al.Sca-1+Lin-CD117-mesenchymal stem/stromal cells induce the generation of novel IRF8-controlled regulatory dendritic cells through Notch-RBP-J signaling[J].J Immunol,2015,194(9):4298-4308.
[19]Murphy T L,Tussiwand R,Murphy K M.Specificity through cooperation:BATF-IRF interactions control immune-regulatory networks[J]Nat Rev Immunol,2013,13(7):499-509.
[20]Garjales-Reyes G E,Iwata A,Albring J,et al.Batf3 maintains autoactivation of Irf8 for commitment of a CD8α+conventional DC clonogenic progenitor[J].Nat Immunol,2015,16(7):708-717.
[21]Park J H,Choi A J,Kim S J,et al.3,3'-Diindolylmethane inhibits Flt3L/GM-CSF-induced-bone marrow-derived CD103+dendritic cell differentiation regulating phosphorylation of STAT3 and STAT5[J].Immune Netw,2015,15(6):278-290.
[22]Jaiswal H,Kaushik M,Sougrat R,et al.Batf3 and Id2 have a synergistic effect on Irf8-directed classical CD8α+dendritic cell development[J].J Immunol,2013,191(12):5993-6001.
[23]Pigin M,Ashok D,Acha-Orbea H.Derivation and utilization of functional CD8+dendritic cell lines[J/OL].Methods Mol Biol,2016,1423:39-49.doi:10.1007/978-1-4939-3606-9_3.
[24]ChauvistréH,Küstermann C,Rehage N,et al.Dendritic cell development requires histone deacetylase activity[J].Eur J Immunol,2014,44(8):2478-2488.
[25]Singh H,Glasmacher E,Chang A B,et al.The molecular choreography of IRF4 and IRF8 with immune system partners[J].Cold Spring Harb Symp Quant Biol,2013,78:101-104.
[26]Paschall A V,Zhang R,Qi C F,et al.IFN regulatory factor 8 represses GM-CSF expression in T cells to affect myeloid cell lineage differentiation[J].J Immunol,2015,194(5):2369-2379.
[27]Yáez A,Ng M Y,Hassanzadeh-Kiabi N,et al.IRF8 acts in lineagecommitted rather than oligopotent progenitors to control neutrophil vsmonocyte production[J/OL].Blood,2015,125(9):1452-1459.
[28]Waight J D,Netherby C,Hensen M L,et al.Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis[J/OL].J Clin Invest,2013,123(10):4464-4478.
[29]Bhattacharya D.Basophils take a slice of IRF8 pie[J].Blood,2015,125(2):214-215.
[30]Scheller M,Schnheit J,Zimmermann K,et al.Cross talk between Wnt/β-catenin and Irf8 in leukemia progression and drug resistance[J].J Exp Med,2013,210(11):2239-2256.
[31]Hu L,Huang W,Hjort E E,et al.The interferon consensus sequence binding protein(Icsbp/Irf8)is required for termination of emergency granulopoiesis[J].J Bio Chem,2016,291(8):4107-4120.
[32]Watanabe T,Hotta C,Koizumi S,et al.The transcription factor IRF8 counteracts BCR-ABL to rescue dendritic cell development in chronic myelogenous leukemia[J].Cancer Res,2013,73(22):6642-6653.
[33]Waight J D,Banik D,Griffiths E A,et al.Regulation of the interferon regulatory factor-8(IRF-8)tumor suppressor gene by the signal transducer and activator of transcription 5(STAT5)transcription factor in chronic myeloid leukemia[J].J Biol Chem,2014,289(22):15642-15652.
[34]Vander Lugt B,Khan A A,Hackney J A,et al.Transcriptional programming of dendritic cells for enhanced MHC classⅡantigen presentation[J].Nat Immunol,2014,15(2):161-167.
[35]Lin J D,Wang Y H,Liu C H,et al.Association of IRF8 gene polymorphisms with autoimmune thyroid disease[J].Eur J Clini Invest,2015,45(7):711-719.
[36]Zhang Q,Zhang L,Li L,et al.Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis[J].Cancer Lett,2014,354(2):227-234.
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