nach oben

International Journal of Hematology

Erschienen in:

01.04.2015 | Progress in Hematology

Regulation of myelopoiesis by the transcription factor IRF8

verfasst von: Tomohiko Tamura, Daisuke Kurotaki, Shin-ichi Koizumi

Erschienen in: International Journal of Hematology | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

Interferon regulatory factor-8 (IRF8) is a transcription factor expressed in hematopoietic cells, particularly in mononuclear phagocytes [monocytes/macrophages and dendritic cells (DCs)] and their progenitors. Various studies have demonstrated that IRF8 is essential for the development of monocytes, DCs, eosinophils, and basophils. Conversely, IRF8 suppresses the generation of neutrophils. Accordingly, Irf8 ^−/− mice develop immunodeficiency and a chronic myeloid leukemia (CML)-like disease. Mutations and loss of expression of the human IRF8 gene are also associated with immunodeficiency and CML, respectively. Recent findings have begun to reveal the transcription factor network and epigenetic changes governed by IRF8. For example, in mononuclear phagocyte progenitors, IRF8 cooperates with PU.1 to promote the formation of promoter-distal enhancers to induce monocyte-related genes including the critical downstream transcription factor gene Klf4. On the other hand, IRF8 blocks C/EBPα activity to suppress the neutrophil differentiation program. Indeed, Irf8 ^−/− mononuclear phagocyte progenitors fail to efficiently generate monocytes and DCs and, instead, aberrantly give rise to neutrophils. This article provides an overview of recent advances in our understanding of the role of IRF8 in myelopoiesis and related diseases.

Driggers PH, Ennist DL, Gleason SL, Mak WH, Marks MS, Levi BZ, et al. An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. Proc Natl Acad Sci USA. 1990;87:3743–7.CrossRefPubMedCentralPubMed

Tamura T, Yanai H, Savitsky D, Taniguchi T. The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol. 2008;26:535–84.CrossRefPubMed

Kanno Y, Levi BZ, Tamura T, Ozato K. Immune cell-specific amplification of interferon signaling by the IRF-4/8-PU.1 complex. J Interferon Cytokine Res. 2005;25:770–9.CrossRefPubMed

Tamura T, Ozato K. ICSBP/IRF-8: its regulatory roles in the development of myeloid cells. J Interferon Cytokine Res. 2002;22:145–52.CrossRefPubMed

Kurotaki D, Osato N, Nishiyama A, Yamamoto M, Ban T, Sato H, et al. Essential role of the IRF8–KLF4 transcription factor cascade in murine monocyte differentiation. Blood. 2013;121:1839–49.CrossRefPubMedCentralPubMed

Murphy TL, Tussiwand R, Murphy KM. Specificity through cooperation: BATF-IRF interactions control immune-regulatory networks. Nat Rev Immunol. 2013;13:499–509.CrossRefPubMed

Holtschke T, Lohler J, Kanno Y, Fehr T, Giese N, Rosenbauer F, et al. Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell. 1996;87:307–17.CrossRefPubMed

Wang H, Morse HC 3rd. IRF8 regulates myeloid and B lymphoid lineage diversification. Immunol Res. 2009;43:109–17.CrossRefPubMedCentralPubMed

Iwasaki H, Akashi K. Myeloid lineage commitment from the hematopoietic stem cell. Immunity. 2007;26:726–40.CrossRefPubMed

10.

Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science. 2010;327:656–61.CrossRefPubMedCentralPubMed

11.

Kurotaki D, Yamamoto M, Nishiyama A, Uno K, Ban T, Ichino M, et al. IRF8 inhibits C/EBPα activity to restrain mononuclear phagocyte progenitors from differentiating into neutrophils. Nat Commun. 2014;5:4978.CrossRefPubMed

12.

Wang H, Yan M, Sun J, Jain S, Yoshimi R, Abolfath SM, et al. A reporter mouse reveals lineage-specific and heterogeneous expression of IRF8 during lymphoid and myeloid cell differentiation. J Immunol. 2014;193:1766–77.CrossRefPubMed

13.

Hettinger J, Richards DM, Hansson J, Barra MM, Joschko AC, Krijgsveld J, et al. Origin of monocytes and macrophages in a committed progenitor. Nat Immunol. 2013;14:821–30.CrossRefPubMed

14.

Onai N, Kurabayashi K, Hosoi-Amaike M, Toyama-Sorimachi N, Matsushima K, Inaba K, et al. A clonogenic progenitor with prominent plasmacytoid dendritic cell developmental potential. Immunity. 2013;38:943–57.CrossRefPubMed

15.

Gautier EL, Shay T, Miller J, Greter M, Jakubzick C, Ivanov S, et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol. 2012;13:1118–28.CrossRefPubMedCentralPubMed

16.

Franco CB, Chen CC, Drukker M, Weissman IL, Galli SJ. Distinguishing mast cell and granulocyte differentiation at the single-cell level. Cell Stem Cell. 2010;6:361–8.CrossRefPubMedCentralPubMed

17.

Sasaki H, Kurotaki D, Osato N, Sato H, Sasaki I, Koizumi S, et al. Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells. Blood. 2015;125:358–69.CrossRefPubMed

18.

Miller JC, Brown BD, Shay T, Gautier EL, Jojic V, Cohain A, et al. Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol. 2012;13:888–99.CrossRefPubMedCentralPubMed

19.

Schonheit J, Kuhl C, Gebhardt ML, Klett FF, Riemke P, Scheller M, et al. PU.1 level-directed chromatin structure remodeling at the Irf8 gene drives dendritic cell commitment. Cell Rep. 2013;3:1617–28.CrossRefPubMed

20.

Scheller M, Foerster J, Heyworth CM, Waring JF, Lohler J, Gilmore GL, et al. Altered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein. Blood. 1999;94:3764–71.PubMed

21.

Tamura T, Nagamura-Inoue T, Shmeltzer Z, Kuwata T, Ozato K. ICSBP directs bipotential myeloid progenitor cells to differentiate into mature macrophages. Immunity. 2000;13:155–65.CrossRefPubMed

22.

Tsujimura H, Nagamura-Inoue T, Tamura T, Ozato K. IFN consensus sequence binding protein/IFN regulatory factor-8 guides bone marrow progenitor cells toward the macrophage lineage. J Immunol. 2002;169:1261–9.CrossRefPubMed

23.

Tamura T, Thotakura P, Tanaka TS, Ko MS, Ozato K. Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. Blood. 2005;106:1938–47.CrossRefPubMedCentralPubMed

24.

Hambleton S, Salem S, Bustamante J, Bigley V, Boisson-Dupuis S, Azevedo J, et al. IRF8 mutations and human dendritic-cell immunodeficiency. N Engl J Med. 2011;365:127–38.CrossRefPubMedCentralPubMed

25.

Alder JK, Georgantas RW 3rd, Hildreth RL, Kaplan IM, Morisot S, Yu X, et al. Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo. J Immunol. 2008;180:5645–52.CrossRefPubMedCentralPubMed

26.

Marquis JF, Kapoustina O, Langlais D, Ruddy R, Dufour CR, Kim BH, et al. Interferon regulatory factor 8 regulates pathways for antigen presentation in myeloid cells and during tuberculosis. PLoS Genet. 2011;7:e1002097.CrossRefPubMedCentralPubMed

27.

Epelman S, Lavine KJ, Randolph GJ. Origin and functions of tissue macrophages. Immunity. 2014;41:21–35.CrossRefPubMed

28.

Yamamoto M, Kato T, Hotta C, Nishiyama A, Kurotaki D, Yoshinari M, et al. Shared and distinct functions of the transcription factors IRF4 and IRF8 in myeloid cell development. PLoS One. 2011;6:e25812.CrossRefPubMedCentralPubMed

29.

Masuda T, Tsuda M, Yoshinaga R, Tozaki-Saitoh H, Ozato K, Tamura T, et al. IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. Cell Rep. 2012;1:334–40.CrossRefPubMedCentralPubMed

30.

Kierdorf K, Erny D, Goldmann T, Sander V, Schulz C, Perdiguero EG, et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat Neurosci. 2013;16:273–80.CrossRefPubMed

31.

Zhao B, Takami M, Yamada A, Wang X, Koga T, Hu X, et al. Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis. Nat Med. 2009;15:1066–71.CrossRefPubMedCentralPubMed

32.

Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, et al. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol. 2014;14:571–8.CrossRefPubMed

33.

Schiavoni G, Mattei F, Borghi P, Sestili P, Venditti M, Morse HC 3rd, et al. ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells. Blood. 2004;103:2221–8.CrossRefPubMed

34.

Chopin M, Seillet C, Chevrier S, Wu L, Wang H, Morse HC 3rd, et al. Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks. J Exp Med. 2013;210:2967–80.CrossRefPubMedCentralPubMed

35.

Schiavoni G, Mattei F, Sestili P, Borghi P, Venditti M, Morse HC 3rd, et al. ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8α⁺ dendritic cells. J Exp Med. 2002;196:1415–25.CrossRefPubMedCentralPubMed

36.

Tsujimura H, Tamura T, Gongora C, Aliberti J, Reis e Sousa C, Sher A, et al. ICSBP/IRF-8 retrovirus transduction rescues dendritic cell development in vitro. Blood. 2003;101:961–9.CrossRefPubMed

37.

Tsujimura H, Tamura T, Ozato K. Cutting edge: IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type I IFN-producing plasmacytoid dendritic cells. J Immunol. 2003;170:1131–5.CrossRefPubMed

38.

Tamura T, Tailor P, Yamaoka K, Kong HJ, Tsujimura H, O’Shea JJ, et al. IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity. J Immunol. 2005;174:2573–81.CrossRefPubMed

39.

Edelson BT, Kc W, Juang R, Kohyama M, Benoit LA, Klekotka PA, et al. Peripheral CD103⁺ dendritic cells form a unified subset developmentally related to CD8α⁺ conventional dendritic cells. J Exp Med. 2010;207:823–36.CrossRefPubMedCentralPubMed

40.

Becker AM, Michael DG, Satpathy AT, Sciammas R, Singh H, Bhattacharya D. IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors. Blood. 2012;119:2003–12.CrossRefPubMedCentralPubMed

41.

Aliberti J, Schulz O, Pennington DJ, Tsujimura H, Reise Sousa C, Ozato K, et al. Essential role for ICSBP in the in vivo development of murine CD8α⁺ dendritic cells. Blood. 2003;101:305–10.CrossRefPubMed

42.

Tailor P, Tamura T, Morse HC 3rd, Ozato K. The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse. Blood. 2008;111:1942–5.CrossRefPubMedCentralPubMed

43.

Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, et al. Batf3 deficiency reveals a critical role for CD8α⁺ dendritic cells in cytotoxic T cell immunity. Science. 2008;322:1097–100.CrossRefPubMedCentralPubMed

44.

Hacker C, Kirsch RD, Ju XS, Hieronymus T, Gust TC, Kuhl C, et al. Transcriptional profiling identifies Id2 function in dendritic cell development. Nat Immunol. 2003;4:380–6.CrossRefPubMed

45.

Jackson JT, Hu Y, Liu R, Masson F, D’Amico A, Carotta S, et al. Id2 expression delineates differential checkpoints in the genetic program of CD8α⁺ and CD103⁺ dendritic cell lineages. EMBO J. 2011;30:2690–704.CrossRefPubMedCentralPubMed

46.

Jaiswal H, Kaushik M, Sougrat R, Gupta M, Dey A, Verma R, et al. Batf3 and Id2 have a synergistic effect on Irf8-directed classical CD8α⁺ dendritic cell development. J Immunol. 2013;191:5993–6001.CrossRefPubMed

47.

Bornstein C, Winter D, Barnett-Itzhaki Z, David E, Kadri S, Garber M, et al. A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin States. Mol Cell. 2014;56:749–62.CrossRefPubMed

48.

Suzuki S, Honma K, Matsuyama T, Suzuki K, Toriyama K, Akitoyo I, et al. Critical roles of interferon regulatory factor 4 in CD11b^highCD8α⁺ dendritic cell development. Proc Natl Acad Sci USA. 2004;101:8981–6.CrossRefPubMedCentralPubMed

49.

Milanovic M, Terszowski G, Struck D, Liesenfeld O, Carstanjen D. IFN consensus sequence binding protein (Icsbp) is critical for eosinophil development. J Immunol. 2008;181:5045–53.CrossRefPubMed

50.

Qi X, Hong J, Chaves L, Zhuang Y, Chen Y, Wang D, et al. Antagonistic regulation by the transcription factors C/EBPα and MITF specifies basophil and mast cell fates. Immunity. 2013;39:97–110.CrossRefPubMedCentralPubMed

51.

Kanno Y, Kozak CA, Schindler C, Driggers PH, Ennist DL, Gleason SL, et al. The genomic structure of the murine ICSBP gene reveals the presence of the gamma interferon-responsive element, to which an ISGF3α subunit (or similar) molecule binds. Mol Cell Biol. 1993;13:3951–63.PubMedCentralPubMed

52.

Cohen SB, Smith NL, McDougal C, Pepper M, Shah S, Yap GS, et al. β-catenin signaling drives differentiation and proinflammatory function of IRF8-dependent dendritic cells. J Immunol. 2015;194:210–22.CrossRefPubMed

53.

Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, Locksley R, et al. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell. 2008;135:37–48.CrossRefPubMedCentralPubMed

54.

Esashi E, Wang YH, Perng O, Qin XF, Liu YJ, Watowich SS. The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8. Immunity. 2008;28:509–20.CrossRefPubMedCentralPubMed

55.

Shimokawa N, Nishiyama C, Nakano N, Maeda K, Suzuki R, Hara M, et al. Suppressive effects of transcription factor GATA-1 on cell type-specific gene expression in dendritic cells. Immunogenetics. 2010;62:421–9.CrossRefPubMed

56.

Vidovic K, Svensson E, Nilsson B, Thuresson B, Olofsson T, Lennartsson A, et al. Wilms’ tumor gene 1 protein represses the expression of the tumor suppressor interferon regulatory factor 8 in human hematopoietic progenitors and in leukemic cells. Leukemia. 2010;24:992–1000.CrossRefPubMed

57.

Waight JD, Netherby C, Hensen ML, Miller A, Hu Q, Liu S, et al. Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis. J Clin Invest. 2013;123:4464–78.CrossRefPubMedCentralPubMed

58.

Schmidt M, Nagel S, Proba J, Thiede C, Ritter M, Waring JF, et al. Lack of interferon consensus sequence binding protein (ICSBP) transcripts in human myeloid leukemias. Blood. 1998;91:22–9.PubMed

59.

Hao SX, Ren R. Expression of interferon consensus sequence binding protein (ICSBP) is downregulated in BCR–ABL-induced murine chronic myelogenous leukemia-like disease, and forced coexpression of ICSBP inhibits Bcr–Abl-induced myeloproliferative disorder. Mol Cell Biol. 2000;20:1149–61.CrossRefPubMedCentralPubMed

60.

Schmidt M, Hochhaus A, Nitsche A, Hehlmann R, Neubauer A. Expression of nuclear transcription factor interferon consensus sequence binding protein in chronic myeloid leukemia correlates with pretreatment risk features and cytogenetic response to interferon-α. Blood. 2001;97:3648–50.CrossRefPubMed

61.

Gabriele L, Phung J, Fukumoto J, Segal D, Wang IM, Giannakakou P, et al. Regulation of apoptosis in myeloid cells by interferon consensus sequence-binding protein. J Exp Med. 1999;190:411–21.CrossRefPubMedCentralPubMed

62.

Tamura T, Kong HJ, Tunyaplin C, Tsujimura H, Calame K, Ozato K. ICSBP/IRF-8 inhibits mitogenic activity of p210 Bcr/Abl in differentiating myeloid progenitor cells. Blood. 2003;102:4547–54.CrossRefPubMed

63.

Schmidt M, Bies J, Tamura T, Ozato K, Wolff L. The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up-regulates expression of tumor suppressor p15^Ink4b in murine myeloid cells. Blood. 2004;103:4142–9.CrossRefPubMed

64.

Burchert A, Cai D, Hofbauer LC, Samuelsson MK, Slater EP, Duyster J, et al. Interferon consensus sequence binding protein (ICSBP; IRF-8) antagonizes BCR/ABL and down-regulates bcl-2. Blood. 2004;103:3480–9.CrossRefPubMed

65.

Schwieger M, Lohler J, Friel J, Scheller M, Horak I, Stocking C. AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency. J Exp Med. 2002;196:1227–40.CrossRefPubMedCentralPubMed

66.

Gurevich RM, Rosten PM, Schwieger M, Stocking C, Humphries RK. Retroviral integration site analysis identifies ICSBP as a collaborating tumor suppressor gene in NUP98-TOP1-induced leukemia. Exp Hematol. 2006;34:1192–201.PubMed

67.

Hara T, Schwieger M, Kazama R, Okamoto S, Minehata K, Ziegler M, et al. Acceleration of chronic myeloproliferation by enforced expression of Meis1 or Meis3 in Icsbp-deficient bone marrow cells. Oncogene. 2008;27:3865–9.CrossRefPubMed

68.

Scheller M, Schonheit J, Zimmermann K, Leser U, Rosenbauer F, Leutz A. Cross talk between Wnt/β-catenin and Irf8 in leukemia progression and drug resistance. J Exp Med. 2013;210:2239–56.CrossRefPubMedCentralPubMed

69.

Huang W, Zhou W, Saberwal G, Konieczna I, Horvath E, Katsoulidis E, et al. Interferon consensus sequence binding protein (ICSBP) decreases β-catenin activity in myeloid cells by repressing GAS2 transcription. Mol Cell Biol. 2010;30:4575–94.CrossRefPubMedCentralPubMed

70.

Deng M, Daley GQ. Expression of interferon consensus sequence binding protein induces potent immunity against BCR/ABL-induced leukemia. Blood. 2001;97:3491–7.CrossRefPubMed

71.

Nardi V, Naveiras O, Azam M, Daley GQ. ICSBP-mediated immune protection against BCR–ABL-induced leukemia requires the CCL6 and CCL9 chemokines. Blood. 2009;113:3813–20.CrossRefPubMedCentralPubMed

72.

Mohty M, Isnardon D, Vey N, Briere F, Blaise D, Olive D, et al. Low blood dendritic cells in chronic myeloid leukaemia patients correlates with loss of CD34⁺/CD38⁻ primitive haematopoietic progenitors. Br J Haematol. 2002;119:115–8.CrossRefPubMed

73.

Boissel N, Rousselot P, Raffoux E, Cayuela JM, Maarek O, Charron D, et al. Defective blood dendritic cells in chronic myeloid leukemia correlate with high plasmatic VEGF and are not normalized by imatinib mesylate. Leukemia. 2004;18:1656–61.CrossRefPubMed

74.

Watanabe T, Hotta C, Koizumi S, Miyashita K, Nakabayashi J, Kurotaki D, et al. The transcription factor IRF8 counteracts BCR–ABL to rescue dendritic cell development in chronic myelogenous leukemia. Cancer Res. 2013;73:6642–53.CrossRefPubMed

75.

Waight JD, Banik D, Griffiths EA, Nemeth MJ, Abrams SI. 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 Biol Chem. 2014;289:15642–52.CrossRefPubMed

76.

Hu X, Yang D, Zimmerman M, Liu F, Yang J, Kannan S, et al. IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia. Cancer Res. 2011;71:2882–91.CrossRefPubMedCentralPubMed

Titel: Regulation of myelopoiesis by the transcription factor IRF8
verfasst von: Tomohiko Tamura
Daisuke Kurotaki
Shin-ichi Koizumi
Publikationsdatum: 01.04.2015
Verlag: Springer Japan
Erschienen in: International Journal of Hematology / Ausgabe 4/2015
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-015-1761-9

Springer Medizin

Regulation of myelopoiesis by the transcription factor IRF8

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2015

Bleeding complications after arthroscopy in a JAK2V617F-positive patient with essential thrombocythemia and acquired von Willebrand syndrome (AVWS)

The International Immune Tolerance Induction Study and its follow-up study on Japanese hemophilia A patients with inhibitors

Massive splenic hamartoma with bizarre stromal cells

C/EBPα in normal and malignant myelopoiesis

Successful pregnancy and delivery via in vitro fertilization with cryopreserved and thawed embryo transfer in an acute myeloid leukemia patient after allogeneic bone marrow transplantation

Evaluation of HNA-expressing cell line-based antigen capture systems and a solid-phase system for detecting HNA-1a antibodies

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie