RESEARCH ARTICLE

Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset

  • Haisheng Yu 1,3 ,
  • Peng Zhang 2,3 ,
  • Xiangyun Yin 1,3 ,
  • Zhao Yin 4 ,
  • Quanxing Shi 4 ,
  • Ya Cui 2 ,
  • Guanyuan Liu 5 ,
  • Shouli Wang 4 ,
  • Pier Paolo Piccaluga 6 ,
  • Taijiao Jiang , 2 ,
  • Liguo Zhang , 1
Expand
  • 1. Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • 2. Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • 3. Graduate School of the Chinese Academy of Sciences, Beijing 100080, China
  • 4. Department of Cardiology, 306th Hospital of PLA, Beijing 100101, China
  • 5. Department of Gynecology and Obstetrics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
  • 6. Department of Experimental, Diagnostic, and Specialty Medicine, Hematopathology & Hematology Sections, Molecular Pathology Laboratory, S. Orsola-Malpighi Hospital, Bologna University, Bologna 40126, Italy

Received date: 10 Dec 2014

Accepted date: 25 Dec 2014

Published date: 13 Apr 2015

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56+ DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56+ DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56+ DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56+ DCs represent a novel mDC subset mixed with some pDC features. A CD4+CD56+ hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56+ DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4+CD56+ neoplasm may be a tumor counterpart of CD56+ mDCs but not pDCs.

Key words: dendritic cells; CD56+ DC; pDC; mDC; BPDCN

Cite this article

Haisheng Yu , Peng Zhang , Xiangyun Yin , Zhao Yin , Quanxing Shi , Ya Cui , Guanyuan Liu , Shouli Wang , Pier Paolo Piccaluga , Taijiao Jiang , Liguo Zhang . Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset[J]. Protein & Cell, 2015 , 6(4) : 297 -306 . DOI: 10.1007/s13238-015-0140-x

1
Adachi M, Maeda K, Takekawa M (1994) High expression of CD56 (N-CAM) in a patient with cutaneous CD4-positive lymphoma. Am J Hematol47(4): 278-282

DOI

2
Alter O, Brown PO, Botstein D (2000) Singular value decomposition for genome-wide expression data processing and modeling. Proc Natl Acad Sci USA97(18): 10101-10106

DOI

3
An HJ, Yoon DH, Kim S (2013) Blastic plasmacytoid dendritic cell neoplasm: a single-center experience. Ann Hematol92(3): 351-356

DOI

4
Brody JP, Allen S, Schulman P (1995) Acute agranular CD4-positive natural killer cell leukemia. Comprehensive clinicopathologic studies including virologic and in vitro culture with inducing agents. Cancer75(10): 2474-2483

DOI

5
Cao W, Rosen DB, Ito T (2006) Plasmacytoid dendritic cellspecific receptor ILT7-Fc epsilonRI gamma inhibits Toll-like receptor-induced interferon production. J Exp Med203(6): 1399-1405

DOI

6
Cella M, Jarrossay D, Facchetti F (1999) Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med5(8): 919-923

DOI

7
Cerboni S, Gentili M, Manel N (2013) Diversity of pathogen sensors in dendritic cells. Adv Immunol120: 211-237

DOI

8
Chaperot L, Bendriss N, Manches O (2001) Identification of a leukemic counterpart of the plasmacytoid dendritic cells. Blood97(10): 3210-3217

DOI

9
Cisse B, Caton ML, Lehner M (2008) Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell135(1): 37-48

DOI

10
Comeau MR (2002) Van der Vuurst de Vries AR, Maliszewski CR, Galibert L. CD123bright plasmacytoid predendritic cells: progenitors undergoing cell fate conversion? J Immunol169(1): 75-83

DOI

11
Defays A, David A, de Gassart A (2011) BAD-LAMP is a novel biomarker of nonactivated human plasmacytoid dendritic cells. Blood118(3): 609-617

DOI

12
Du P, Kibbe WA, Lin SM (2008) lumi: a pipeline for processing Illumina microarray. Bioinformatics24(13): 1547-1548

DOI

13
Dzionek A, Fuchs A, Schmidt P (2000) BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol165(11): 6037-6046

DOI

14
Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA95(25): 14863-14868

DOI

15
Esashi E, Bao M, Wang YH, Cao W, Liu YJ (2012) PACSIN1 regulates the TLR7/9-mediated type I interferon response in plasmacytoid dendritic cells. Eur J Immunol42(3): 573-579

DOI

16
Facchetti F, Jones D, Petrella T (2008) Blastic plasmacytoid dendritic cell neoplasm. In: Swerdlow S, Campo E, Harris N (eds) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. International Agency for Research on Cancer (IARC), Lyon, pp 145-147

DOI

17
Ghosh HS, Cisse B, Bunin A, Lewis KL, Reizis B (2010) Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity33(6): 905-916

DOI

18
Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J, Liu YJ (1997) The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J Exp Med185(6): 1101-1111

DOI

19
Herling M, Teitell MA, Shen RR, Medeiros LJ, Jones D (2003) TCL1 expression in plasmacytoid dendritic cells (DC2s) and the related CD4+ CD56+ blastic tumors of skin. Blood101(12): 5007-5009

DOI

20
Kadowaki N, Ho S, Antonenko S (2001) Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med194(6): 863-869

DOI

21
Liu YJ (2005) IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol23: 275-306

DOI

22
Marafioti T, Paterson JC, Ballabio E (2008) Novel markers of normal and neoplastic human plasmacytoid dendritic cells. Blood111(7): 3778-3792

DOI

23
Maric M, Arunachalam B, Phan UT (2001) Defective antigen processing in GILT-free mice. Science294(5545): 1361-1365

DOI

24
Matsui T, Connolly JE, Michnevitz M (2009) CD2 distinguishes two subsets of human plasmacytoid dendritic cells with distinct phenotype and functions. J Immunol182(11): 6815-6823

DOI

25
Petrella T, Facchetti F (2010) Tumoral aspects of plasmacytoid dendritic cells: what do we know in 2009? Autoimmunity43(3): 210-214

DOI

26
Petrella T, Dalac S, Maynadie M (1999) CD4+ CD56+ cutaneous neoplasms: a distinct hematological entity? Groupe Francais d’Etude des Lymphomes Cutanes (GFELC). Am J Surg Pathol23(2): 137-146

DOI

27
Petrella T, Comeau MR, Maynadie M (2002) ‘Agranular CD4+ CD56+ hematodermic neoplasm’ (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes. Am J Surg Pathol26(7): 852-862

DOI

28
Pilichowska ME, Fleming MD, Pinkus JL, Pinkus GS (2007) CD4+/ CD56+ hematodermic neoplasm (“blastic natural killer cell lymphoma”): neoplastic cells express the immature dendritic cell marker BDCA-2 and produce interferon. Am J Clin Pathol128(3): 445-453

DOI

29
Rissoan MC, Duhen T, Bridon JM (2002) Subtractive hybridization reveals the expression of immunoglobulin-like transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells. Blood100(9): 3295-3303

DOI

30
Robbins SH, Walzer T, Dembele D (2008) Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling. Genome Biol9(1): R17

DOI

31
Sapienza MR, Fuligni F, Agostinelli C (2014) Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition. Leukemia28: 1606-1616

DOI

32
Schotte R, Nagasawa M, Weijer K, Spits H, Blom B (2004) The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development. J Exp Med200(11): 1503-1509

DOI

33
Siegal FP, Kadowaki N, Shodell M (1999) The nature of the principal type 1 interferon-producing cells in human blood. Science284(5421): 1835-1837

DOI

34
Singh R, Cresswell P (2010) Defective cross-presentation of viral antigens in GILT-free mice. Science328(5984): 1394-1398

DOI

35
Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol3: 1-25

DOI

36
Steinman RM (2007) Lasker Basic Medical Research Award. Dendritic cells: versatile controllers of the immune system. Nat Med13(10): 1155-1159

DOI

37
Trapnell C, Pachter L, Salzberg SL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics25(9): 1105-1111

DOI

38
Uchiyama N, Ito K, Kawai K, Sakamoto F, Takaki M, Ito M (1998) CD2-, CD4+, CD56+ agranular natural killer cell lymphoma of the skin. Am J Dermatopathol20(5): 513-517

DOI

39
Vermi W, Facchetti F, Rosati S (2004) Nodal and extranodal tumor-forming accumulation of plasmacytoid monocytes/interferon-producing cells associated with myeloid disorders. Am J Surg Pathol28(5): 585-595

DOI

40
Ziegler-Heitbrock L, Ancuta P, Crowe S (2010) Nomenclature of monocytes and dendritic cells in blood. Blood116(16): e74-e80

Outlines

/