• Principal Investigator
  • Female

Dr. B. Blom

Position:
Main activities: Teaching, Research
Specialisation:
foto B. Blom is one of the AMC Principal Investigators
Focus of research:

Role of transcription factors, microRNAs and cytokines in the development of the human immune system, including T cells, NK cells, B cells, dendritic cells (DCs) and innate lymphocytes (ILCs). A particular focus is on the molecular requirements that control the development and function of a subset of DC, the plasmacytoid DCs. Their prime function is in the defense against virusses by production of copius amounts of type I Interferons. Aberrant pDC responses are associated with autoimmune diseases, such as lupus.

AMC themes: Infection & Immunity
Departments: Cell Biology and Histology, Experimental Immunology
Douaisi M, Resop RS, Nagasawa M, Craft J, Jamieson BD, Blom B, Uittenbogaart CH, CD31, a Valuable Marker to Identify Early and Late Stages of T Cell Differentiation in the Human Thymus. J IMMUNOL 2017;198 (6):2310-2319 [PubMed]
Nagasawa M, Germar K, Blom B, Spits H, Human CD5(+) Innate Lymphoid Cells Are Functionally Immature and Their Development from CD34(+) Progenitor Cells Is Regulated by Id2. FRONT IMMUNOL 2017;8:1047 [PubMed]
Shikhagaie MM, Björklund ÅK, Mjösberg J , Erjefält JS, Cornelissen AS, Ros XR, Bal SM, Koning JJ, Mebius RE, Mori M, Bruchard M, Blom B, Spits H, Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates. CELL REP 2017;18 (7):1761-1773 [PubMed]
Bernink JH. The biology of human innate lymphoid cells. S.l.: s.n.; 2016. 173p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): Blom B)
Flór TB, Blom B, Pathogens Use and Abuse MicroRNAs to Deceive the Immune System. INT J MOL SCI 2016;17 (4):538 [PubMed]
Resop RS, Douaisi M, Craft J, Jachimowski LCM, Blom B, Uittenbogaart CH, Sphingosine-1-phosphate/sphingosine-1-phosphate receptor 1 signaling is required for migration of naive human T cells from the thymus to the periphery. J ALLERGY CLIN IMMUN 2016;138 (2):551-557.e8 [PubMed]
Bernink JH, Krabbendam L, Germar K, de Jong E, Gronke K, Kofoed-Nielsen M, Munneke JM, Hazenberg MD, Villaudy J, Buskens CJ, Bemelman WA, Diefenbach A, Blom B, Spits H, Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria. IMMUNITY 2015;43 (1):146-160 [PubMed]
Epeldegui M, Blom B, Uittenbogaart CH, BST2/Tetherin is constitutively expressed on human thymocytes with the phenotype and function of Treg cells. EUR J IMMUNOL 2015;45 (3):728-737 [PubMed]
Jachimowski LCM. Regulation of the multifaceted functions of human plasmacytoid dendritic cells: a polyphonic policy. S.l.: s.n.; 2015. 184p. ISBN 978-94-6182-538-4 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H, Uittenbogaart CH; copromotor(s): Blom B)
Karrich JJ, Jachimowski LCM, Uittenbogaart CH, Blom B, The plasmacytoid dendritic cell as the Swiss army knife of the immune system: molecular regulation of its multifaceted functions. J IMMUNOL 2014;193 (12):5772-5778 [PubMed]
Munneke JM, Björklund AT, Mjösberg JM, Garming-Legert K, Bernink JH, Blom B, Huisman C, van Oers MHJ, Spits H, Malmberg KJ, Hazenberg MD, Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. BLOOD 2014;124 (5):812-821 [PubMed]
Centlivre M, Legrand N, Klamer S, Liu YP, Eije KJv, Bohne M, Rijnstra ESv, Weijer K, Blom B, Voermans C, Spits H, Berkhout B, Preclinical In Vivo Evaluation of the Safety of a Multi-shRNA-based Gene Therapy Against HIV-1. MOL THER-NUCL ACIDS 2013;2:e120 [PubMed]
de Jong VM, Abreu JRF, Verrijn Stuart AA, van der Slik AR, Verhaeghen K, Engelse MA, Blom B, Staal FJT, Gorus FK, Roep BO, Alternative splicing and differential expression of the islet autoantigen IGRP between pancreas and thymus contributes to immunogenicity of pancreatic islets but not diabetogenicity in humans. DIABETOLOGIA 2013;56 (12):2651-2658 [PubMed]
Gentek R, Munneke JM, Helbig C, Blom B, Hazenberg MD, Spits H, Amsen D, Modulation of signal strength switches Notch from an inducer of T cells to an inducer of ILC2. FRONT IMMUNOL 2013;4:UNSP 334 [PubMed]
Karrich JJ. Plasmacytoid dendritic cells: how to control the good, the bad, the ugly at the molecular level. s.l.: s.n.; 2013. 192p. ISBN 9789461822314 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): Blom B)
Karrich JJ, Jachimowski LCM, Libouban M, Iyer A, Brandwijk K, Taanman-Kueter EW, Nagasawa M, de Jong EC, Uittenbogaart CH, Blom B, MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic cells. BLOOD 2013;122 (17):3001-3009 [PubMed]
Karrich JJ, Jachimowski LCM, Nagasawa M, Kamp A, Balzarolo M, Wolkers MC, Uittenbogaart CH, van Ham SM, Blom B, IL-21-stimulated human plasmacytoid dendritic cells secrete granzyme B, which impairs their capacity to induce T-cell proliferation. BLOOD 2013;121 (16):3103-3111 [PubMed]
Balzarolo M, Karrich JJ, Engels S, Blom B, Medema JP, Wolkers MC, The transcriptional regulator NAB2 reveals a two-step induction of TRAIL in activated plasmacytoid DCs. EUR J IMMUNOL 2012;42 (11):3019-3027 [PubMed]
Blom B. New Insights in the Development of Human B Lymphocytes in: Anagnostou D, Matutes E, editors. Bone marrow lymphoid infiltrates : Diagnosis and clinical impact. Berlin: Springer; 2012., p. 1-15
Diehl SA, Schmidlin H, Nagasawa M, Blom B, Spits H, IL-6 Triggers IL-21 production by human CD4(+) T cells to drive STAT3-dependent plasma cell differentiation in B cells. IMMUNOL CELL BIOL 2012;90 (8):802-811 [PubMed]
Karrich JJ, Balzarolo M, Schmidlin H, Libouban M, Nagasawa M, Gentek R, Kamihira S, Maeda T, Amsen D, Wolkers MC, Blom B, The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the antiapoptotic gene BCL2-A1. BLOOD 2012;119 (22):5191-5200 [PubMed]
Legrand N, van der Velden GJ, Fang RHT, Douaisi M, Weijer K, Das AT, Blom B, Uittenbogaart CH, Berkhout B, Centlivre M, A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4(+) T-cell depletion. J GEN VIROL 2012;93 (9):2017-2027 [PubMed]
Mjösberg J , Bernink J, Golebski K, Karrich JJ, Peters CP, Blom B, te Velde AA, Fokkens WJ, van Drunen CM, Spits H, The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. IMMUNITY 2012;37 (4):649-659 [PubMed]
Yusuf D, Butland SL, Swanson MI, Bolotin E, Ticoll A, Cheung WA, Zhang XYC, Dickman CTD, Fulton DL, Lim JS, Schnabl JM, Ramos OHP, Vasseur-Cognet M, de Leeuw CN, Simpson EM, Ryffel GU, Lam EWF, Kist R, Wilson MSC, Marco-Ferreres R, Brosens JJ, Beccari LL, Bovolenta P, Benayoun BA, Monteiro LJ, Schwenen HDC, Grontved L, Wederell E, Mandrup S, Veitia RA, Chakravarthy H, Hoodless PA, Mancarelli MM, Torbett BE, Banham AH, Reddy SP, Cullum RL, Liedtke M, Tschan MP, Vaz M, Rizzino A, Zannini M, Frietze S, Farnham PJ, Eijkelenboom A, Brown PJ, Laperrière D, Leprince D, de Cristofaro T, Prince KL, Putker M, del Peso L, Camenisch G, Wenger RH, Mikula M, Rozendaal M, Mader S, Ostrowski J, Rhodes SJ, van Rechem C, Boulay G, Olechnowicz SWZ, Breslin MB, Lan MS, Nanan KK, Wegner M, Hou J, Mullen RD, Colvin SC, Noy PJ, Webb CF, Witek ME, Ferrell S, Daniel JM, Park J, Waldman SA, Peet DJ, Taggart M, Jayaraman PS, Karrich JJ, Blom B, Vesuna F, O'Geen H, Sun Y, Gronostajski RM, Woodcroft MW, Hough MR, Chen E, Europe-Finner GN, Karolczak-Bayatti M, Bailey J, Hankinson O, Raman V, Lebrun DP, Biswal S, Harvey CJ, Debruyne JP, Hogenesch JB, Hevner RF, Héligon C, Luo XM, Blank MC, Millen KJ, Sharlin DS, Forrest D, Dahlman-Wright K, Zhao C, Mishima Y, Sinha S, Chakrabarti R, Portales-Casamar E, Sladek FM, Bradley PH, Wasserman WW, The Transcription Factor Encyclopedia. GENOME BIOL 2012;13 (3):R24 [PubMed]
Colantonio AD, Epeldegui M, Jesiak M, Jachimowski L, Blom B, Uittenbogaart CH, IFN-α is constitutively expressed in the human thymus, but not in peripheral lymphoid organs. PLOS ONE 2011;6 (8):e24252 [PubMed]
Centlivre M, Zhou X, Pouw SM, Weijer K, Kleibeuker W, Das AT, Blom B, Seppen J, Berkhout B, Legrand N, Autoregulatory lentiviral vectors allow multiple cycles of doxycycline-inducible gene expression in human hematopoietic cells in vivo. GENE THER 2010;17 (1):14-25 [PubMed]
Scheeren FA, van Lent AU, Nagasawa M, Weijer K, Spits H, Legrand N, Blom B, Thymic stromal lymphopoietin induces early human B-cell proliferation and differentiation. EUR J IMMUNOL 2010;40 (4):955-965 [PubMed]
Schotte R, Dontje W, Nagasawa M, Yasuda Y, Bakker AQ, Spits H, Blom B, Synergy between IL-15 and Id2 Promotes the Expansion of Human NK Progenitor Cells, Which Can Be Counteracted by the E Protein HEB Required To Drive T Cell Development. J IMMUNOL 2010;184 (12):6670-6679 [PubMed]
Schotte R, Schmidlin H, Nagasawa M, Dontje W, Karrich JJ, Uittenbogaart C, Spits H, Blom B, Isolation and in vitro generation of gene-manipulated human plasmacytoid and conventional dendritic cells. METHODS MOL BIOL 2010;595:67-85 [PubMed]
van Lent AU, Centlivre M, Nagasawa M, Karrich JJ, Pouw SM, Weijer K, Spits H, Blom B, Legrand N, In vivo modulation of gene expression by lentiviral transduction in "human immune system" Rag2-/- gamma c -/- mice. METHODS MOL BIOL 2010;595:87-115 [PubMed]
Schmidlin H, Diehl SA, Blom B, New insights into the regulation of human B-cell differentiation. TRENDS IMMUNOL 2009;30 (6):277-285 [PubMed]
ter Brake O, Legrand N, von Eije KJ, Centlivre M, Spits H, Weijer K, Blom B, Berkhout B, Evaluation of safety and efficacy of RNAi against HIV-1 in the human immune system (Rag-2(-/-)gammac(-/-)) mouse model. GENE THER 2009;16 (1):148-153 [PubMed]
van Lent AU, Dontje W, Nagasawa M, Siamari R, Bakker AQ, Pouw SM, Maijoor KA, Weijer K, Cornelissen JJ, Blom B, Di Santo JP, Spits H, Legrand N, IL-7 Enhances Thymic Human T Cell Development in "Human Immune System" Rag2-/-IL-2R{gamma}c-/- Mice without Affecting Peripheral T Cell Homeostasis. J IMMUNOL 2009;183 (12):7645-7655 [PubMed]
van Lent AUG, Centlivre M, Nagasawa M, Karrich J J., Pouw SM, Weijer K, Spits H, Blom B. In Vivo Modulation of gene expression by Lentiviral Transduction in "Human Immune System" Rag2-/-yc-/-Mice in: Naik SH, editor. Dendritic Cell Protocols. S.l.: Humana Press; 2009. Chapter 6, p. 87-115
Yoon SO, Zhang X, Berner P, Blom B, Choi YS, Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis. J IMMUNOL 2009;183 (1):352-358 [PubMed]
Boniface K, Blom B, Liu YJ, de Waal Malefyt R, From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited. IMMUNOL REV 2008;226 (1):132-146 [PubMed]
Dontje W. From progenitor cell to immune cell: Cytokines and transcription factors in human hematopoietic development.. s.l.: s.n.; 2008. 187p. ISBN - [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H, Blom B; copromotor(s): )
Nagasawa M, Schmidlin H, Hazekamp MG, Schotte R, Blom B, Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and the Ets factor Spi-B. EUR J IMMUNOL 2008;38 (9):2389-2400 [PubMed]
Scheeren FA, Diehl SA, Smit LA, Beaumont T, Naspetti M, Bende RJ, Blom B, Karube K, Ohshima K, van Noesel CJM, Spits H, IL-21 is expressed in Hodgkin lymphoma and activates STAT5: evidence that activated STAT5 is required for Hodgkin lymphomagenesis. BLOOD 2008;111 (9):4706-4715 [PubMed]
Schmidlin H. Transcriptional control of human plasmacytoid dendritic cell and B cell differentiation.. s.l.: s.n.; 2008. 189p. ISBN - [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H, Uittenbogaart CH; copromotor(s): Blom B)
Schmidlin H, Diehl SA, Nagasawa M, Scheeren FA, Schotte R, Uittenbogaart CH, Spits H, Blom B, Spi-B inhibits human plasma cell differentiation by repressing BLIMP1 and XBP-1 expression. BLOOD 2008;112 (5):1804-1812 [PubMed]
An DS, Poon B, Tsong Fang RH, Weijer K, Blom B, Spits H, Chen ISY, Uittenbogaart CH, Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection. CLIN VACCINE IMMUNOL 2007;14 (4):391-396 [PubMed]
Legrand N, Dontje W, van Lent AU, Spits H, Blom B, Human thymus regeneration and T cell reconstitution. SEMIN IMMUNOL 2007;19 (5):280-288 [PubMed]
Schotte R. Control of early human lymphoid development. S.l.: s.n.; 2007. 148p. ISBN 9789090212191 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): Blom B)
Blom B, Spits H, Development of human lymphoid cells. ANNU REV IMMUNOL 2006;24:287-320 [PubMed]
Dontje W, Schotte R, Cupedo T, Nagasawa M, Scheeren F, Gimeno R, Spits H, Blom B, Delta-like1-induced Notch1 signaling regulates the human plasmacytoid dendritic cell versus T-cell lineage decision through control of GATA-3 and Spi-B. BLOOD 2006;107 (6):2446-2452 [PubMed]
Overwijk WW, de Visser KE, Tirion FH, de Jong LA, Pols TWH, van der Velden YU, van den Boorn JG, Keller AM, Buurman WA, Theoret MR, Blom B, Restifo NP, Kruisbeek AM, Kastelein RA, Haanen JBAG, Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant. J IMMUNOL 2006;176 (9):5213-5222 [PubMed]
Schmidlin H, Dontje W, Groot F, Ligthart SJ, Colantonio AD, Oud ME, Schilder-Tol EJ, Spaargaren M, Spits H, Uittenbogaart CH, Blom B, Stimulated plasmacytoid dendritic cells impair human T-cell development. BLOOD 2006;108 (12):3792-3800 [PubMed]
Cupedo T, Nagasawa M, Weijer K, Blom B, Spits H, Development and activation of regulatory T cells in the human fetus. EUR J IMMUNOL 2005;35 (2):383-390 [PubMed]
Scheeren FA, Naspetti M, Diehl S, Schotte R, Nagasawa M, Wijnands E, Gimeno R, Vyth-Dreese FA, Blom B, Spits H, STAT5 regulates the self-renewal capacity and differentiation of human memory B cells and controls Bcl-6 expression. NAT IMMUNOL 2005;6 (3):303-313 [PubMed]
Chen W, Antonenko S, Sederstrom JM, Liang X, Chan ASH, Kanzler H, Blom B, Blazar BR, Liu YJ, Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. BLOOD 2004;103 (7):2547-2553 [PubMed]
Gimeno R, Weijer K, Voordouw A, Uittenbogaart CH, Legrand N, Alves NL, Wijnands E, Blom B, Spits H, Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- gammac-/- mice: functional inactivation of p53 in developing T cells. BLOOD 2004;104 (13):3886-3893 [PubMed]
Gurney KB, Colantonio AD, Blom B, Spits H, Uittenbogaart CH, Endogenous IFN-alpha production by plasmacytoid dendritic cells exerts an antiviral effect on thymic HIV-1 infection. J IMMUNOL 2004;173 (12):7269-7276 [PubMed]
Schotte R, Nagasawa M, Weijer K, Spits H, Blom B, The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development. J EXP MED 2004;200 (11):1503-1509 [PubMed]
Blom B, Ligthart SJWC, Schotte R, Spits H, Developmental origin of pre-DC2. HUM IMMUNOL 2002;63 (12):1072-1080 [PubMed]
Weijer K, Uittenbogaart CH, Voordouw A, Couwenberg F, Seppen J, Blom B, Vyth-Dreese FA, Spits H, Intrathymic and extrathymic development of human plasmacytoid dendritic cell precursors in vivo. BLOOD 2002;99 (8):2752-2759 [PubMed]
Blom B, Heemskerk MH, Verschuren MC, van Dongen JJ, Stegmann AP, Bakker AQ, Couwenberg F, Res PC, Spits H, Disruption of alpha beta but not of gamma delta T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors. EMBO J 1999;18 (10):2793-2802 [PubMed]
Blom B, Verschuren MC, Heemskerk MH, Bakker AQ, van Gastel-Mol EJ, Wolvers-Tettero IL, van Dongen JJ, Spits H, TCR gene rearrangements and expression of the pre-T cell receptor complex during human T-cell differentiation. BLOOD 1999;93 (9):3033-3043 [PubMed]
Jacobs H, Krimpenfort P, Haks M, Allen J, Blom B, Démollière C, Kruisbeek A, Spits H, Berns A, PIM1 reconstitutes thymus cellularity in interleukin 7- and common gamma chain-mutant mice and permits thymocyte maturation in Rag- but not CD3gamma-deficient mice. J EXP MED 1999;190 (8):1059-1068 [PubMed]
Blom B, Res PC, Spits H, T cell precursors in man and mice. CRIT REV IMMUNOL 1998;18 (4):371-388 [PubMed]
Spits H, Blom B, Jaleco AC, Weijer K, Verschuren MC, van Dongen JJ, Heemskerk MH, Res PC, Early stages in the development of human T, natural killer and thymic dendritic cells. IMMUNOL REV 1998;165:75-86 [PubMed]
Verschuren MC, Blom B, Bogers AJ, Spits H, van Dongen JJ, PJA-BP expression and TCR delta deletion during human T cell differentiation. INT IMMUNOL 1998;10 (12):1873-1880 [PubMed]
Blom B, Res P, Noteboom E, Weijer K, Spits H, Prethymic CD34+ progenitors capable of developing into T cells are not committed to the T cell lineage. J IMMUNOL 1997;158 (8):3571-3577 [PubMed]
Heemskerk MH, Blom B, Nolan G, Stegmann AP, Bakker AQ, Weijer K, Res PC, Spits H, Inhibition of T cell and promotion of natural killer cell development by the dominant negative helix loop helix factor Id3. J EXP MED 1997;186 (9):1597-1602 [PubMed]
Jaleco AC, Blom B, Res P, Weijer K, Lanier LL, Phillips JH, Spits H, Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells. J IMMUNOL 1997;159 (2):694-702 [PubMed]
Res P, Blom B, Hori T, Weijer K, Spits H, Downregulation of CD1 marks acquisition of functional maturation of human thymocytes and defines a control point in late stages of human T cell development. J EXP MED 1997;185 (1):141-151 [PubMed]
Key publications

Karrich JJ, Jachimowski LCM, Libouban M, Iyer A, Brandwijk K, Taanman-Kueter EW, Nagasawa M, de Jong EC, Uittenbogaart CH, Blom B, MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic cells. BLOOD 2013;122 (17):3001-3009 [PubMed]
Karrich JJ, Jachimowski LCM, Nagasawa M, Kamp A, Balzarolo M, Wolkers MC, Uittenbogaart CH, van Ham SM, Blom B, IL-21-stimulated human plasmacytoid dendritic cells secrete granzyme B, which impairs their capacity to induce T-cell proliferation. BLOOD 2013;121 (16):3103-3111 [PubMed]
Karrich JJ, Balzarolo M, Schmidlin H, Libouban M, Nagasawa M, Gentek R, Kamihira S, Maeda T, Amsen D, Wolkers MC, Blom B, The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the antiapoptotic gene BCL2-A1. BLOOD 2012;119 (22):5191-5200 [PubMed]
Karrich JJ, Jachimowski LCM, Uittenbogaart CH, Blom B, The plasmacytoid dendritic cell as the Swiss army knife of the immune system: molecular regulation of its multifaceted functions. J IMMUNOL 2014;193 (12):5772-5778 [PubMed]
Flór TB, Blom B, Pathogens Use and Abuse MicroRNAs to Deceive the Immune System. INT J MOL SCI 2016;17 (4):538 [PubMed]


All Publications

Curriculum Vitae

 Positions and Employment:

1993-1997:     PhD student, Netherlands Cancer Institute, Amsterdam

1997-2000:     Postdoctoral fellow, Schering at DNAX (owned by Schering Plough), Palo Alto, CA USA

2000-2003:     Senior Postdoc, Netherlands Cancer Institute, Amsterdam

2003-2006:     Assistant Professor, Amsterdam Medical Center/University of Amsterdam, Amsterdam

2006-present: Associate Professor, Amsterdam Medical Center/University of Amsterdam, Amsterdam

2010-present: Principal Investigator, Amsterdam Medical Center/University of Amsterdam, Amsterdam

2015-present: Principal Educator, Amsterdam Medical Center/University of Amsterdam, Amsterdam

2016-present: Head of the HIS mouse facility, Amsterdam Medical Center/University of Amsterdam, Amsterdam

Research programmes

Development and function of human innate lymphoid cells

Our immune system develops from hematopoietic stem cells, which through sequential steps commit into mature effector cells. These processes are tightly regulated by cytokines and transcription factors that enforce lineage decisions. Our main objective focusses on the development and function of the lymphoid compartment, including T, B, Natural Killer (NK), and Dendritic Cells (DC) (Blom & Spits, Annu Rev Immunol. 2006). The cytokines that we consider of interest in this context include IL-7, TSLP, FLT3L, IL-15, and IL-21. The families of transcription factors that we study include members of the STAT, Notch, GATA, and Ets families.

The plasmacytoid DC (pDC) versus T-cell lineage decision in the human thymus is controlled by the balance between the transcription factors Spi-B and GATA-3. Engagement of Notch1, required for T cell development, by Delta-like1 downregulates Spi-B expression, while it induces GATA-3 levels. Consequently, Notch triggering blocks pDC development from progenitor cells, but this can be rescued by ectopically expressing Spi-B (Dontje et al., Blood, 2006).

PDCs are the major type I IFN producing cells after engagement by virusses or TLR agonists. PDC localize among others in the thymus where T cells develop from hematopoietic progenitor cells. We have shown that IFN-alpha strongly impairs development of progenitor cells into T-cells at the level of IL-7R signaling (Schmidlin et al., Blood, 2006). In addition, we showed that thymic pDCs, but not peripheral pDCs, constitutively produce IFN-alpha, which may help to control T cell development (Colantonio et al., Plos One, 2011).

We identified that the transcription factor Spi-B is key in the development of hematopoietic progenitor cells into pDCs (Schotte et al., J Exp Med, 2004). More recent we showed that Spi-B directly regulates the anti-apoptotic gene Bcl2-A1 (Karrich et al., Blood, 2012). Furthermore, we reported that the cytokine IL-21, which is mainly produced by activated CD4+ T cells, stimulates pDCs to secrete high levels of Granzyme B (Karrich et al., Blood, 2013). Granzyme B directly affects the proliferation of T cells and hence may be used in a negative feedback loop to downregulate T cell responses.

A novel layer of regulation that we investigate in pDCs involves the role of microRNAs, which are an evolutionary conserved class of endogenous ~19 to 23-nucleotides long non-coding RNAs.19 They act by repressing gene expression through targeting of the 3’-untranslated region (UTR) of mRNAs resulting in either mRNA degradation or translation inhibition, or a combination of both. We observed that miRNA-146a expression is induced upon TLR triggering and consequently interferes with type I IFN production as well as maturation and survival of pDCs (Karrich et al., Blood in press). 

Theme: Infection and Immunity

Faculty
Dr. B. Blom

PhD Students
K. Liu MD
M. Nagasawa
S.Z. Omar

Others
Drs. K.I.M. Brandwijk

Dr. M.D. Hazenberg MD PhD (Innate and adaptive immunity following allogeneic hematopoietic stem cell transplantation)

Other research related activities
  • Contribution to training of professionals, University of Amsterdam
  • Contribution to training of professionals, VU University Medical Center
  • Membership of medical or scientific committee, University of Amsterdam, HIS mouse facility
  • Membership of medical or scientific committee, University of Amsterdam, User Cie Flowcytometrie
Current research funding
  • None reported