Identification and Characterization of Two Human Monocyte-Derived Dendritic Cell Subpopulations with Different Functions in Dying Cell Clearance and Different Patterns of Cell Death.
Human monocyte-derived dendritic cells (mdDCs) are versatile cells that are used widely for research and experimental therapies. Although different culture conditions can affect their characteristics, there are no known subpopulations. Since monocytes differentiate into dendritic cells (DCs) in a variety of tissues and contexts, we asked whether they can give rise to different subpopulations. In this work we set out to characterize two human mdDC subpopulations that we identified and termed small (DC-S) and large (DC-L). Morphologically, DC-L are larger, more granular and have a more complex cell membrane. Phenotypically, DC-L show higher expression of a wide panel of surface molecules and stronger responses to maturation stimuli. Transcriptomic analysis confirmed their separate identities and findings were consistent with the phenotypes observed. Although they show similar apoptotic cell uptake, DC-L have different capabilities for phagocytosis, demonstrate better antigen processing, and have significantly better necrotic cell uptake. These subpopulations also have different patterns of cell death, with DC-L presenting an inflammatory, "dangerous" phenotype while DC-S mostly downregulate their surface markers upon cell death. Apoptotic cells induce an immune-suppressed phenotype, which becomes more pronounced among DC-L, especially after the addition of lipopolysaccharide. We propose that these two subpopulations correspond to inflammatory (DC-L) and steady-state (DC-S) DC classes that have been previously described in mice and humans.
The Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Uriel
http://orcid.org/0000-0001-9103-2494
U
Trahtemberg
The Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Amir
A
Grau
The Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Adi
A
Tabib
The Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Mizhir
M
Atallah
The Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Alon
A
Krispin
The Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Dror
D
Mevorach
Front Immunol. 2013 Apr 03;4:82
23565116
Adv Immunol. 2013;120:69-103
24070381
Adv Immunol. 2010;108:111-65
21056730
J Immunol. 2002 Feb 1;168(3):1131-8
11801647
Semin Immunol. 1998 Oct;10(5):399-415
9840976
Front Immunol. 2014 Apr 01;5:131
24744755
Nat Immunol. 2009 Dec;10(12):1237-44
19915624
Immunity. 2013 Jul 25;39(1):38-48
23890062
Annu Rev Immunol. 2013;31:563-604
23516985
Immunol Rev. 2010 Mar;234(1):45-54
20193011
Nat Immunol. 2012 Dec;13(12):1145-54
23160217
Cytometry. 1995 Nov 1;21(3):265-74
8582249
Immunol Rev. 2010 Mar;234(1):90-104
20193014
Cold Spring Harb Perspect Biol. 2012 Aug 01;4(8):a007401
22855722
Nat Rev Immunol. 2011 Jan;11(1):21-33
21179118
J Exp Med. 2002 Dec 16;196(12):1553-61
12486098
J Immunol. 2000 Oct 1;165(7):3584-91
11034359
Semin Cell Dev Biol. 2015 May;41:39-48
24910448
Cytometry. 2000 Dec 1;41(4):261-70
11084611
Apoptosis. 2007 Oct;12(10):1769-80
17578666
J Exp Med. 2010 Jun 7;207(6):1131-4
20513744
Science. 2009 Apr 17;324(5925):392-7
19286519
J Immunol. 2010 Jul 15;185(2):795-802
20601611
Annu Rev Immunol. 2015;33:563-606
25665078
Annu Rev Immunol. 2013;31:743-91
23330953
Immunity. 2014 May 15;40(5):642-56
24837101
Curr Opin Immunol. 2014 Feb;26:90-9
24556405
Immunology. 2013 Sep;140(1):22-30
23621371
Annu Rev Immunol. 2009;27:669-92
19132917
Immunol Rev. 2010 Jul;236:11-27
20636805
Blood. 2011 Sep 22;118(12):3311-20
21813450
Int Rev Immunol. 2010 Apr;29(2):111-8
20367138
Nat Rev Immunol. 2009 May;9(5):353-63
19365408
EMBO J. 2014 May 16;33(10):1104-16
24737868
Nature. 2009 Apr 16;458(7240):899-903
19219027
Cell. 2010 Oct 29;143(3):416-29
21029863
Immunity. 2009 Sep 18;31(3):502-12
19733097
Nat Rev Immunol. 2010 Apr;10(4):225-35
20336151
Immunity. 2003 Jul;19(1):71-82
12871640
Cytometry A. 2006 Apr;69(4):240-8
16528734
Blood. 2006 Nov 15;108(10):3580-9
16882710
Nature. 1998 Mar 19;392(6673):245-52
9521319
Immunity. 2011 Oct 28;35(4):456-66
22035838
Immunity. 2007 May;26(5):629-41
17509906
Trends Biotechnol. 2014 Sep;32(9):456-65
24998519
Exp Mol Pathol. 2004 Oct;77(2):104-15
15351233
Cytometry. 1997 Jul 1;28(3):253-63
9222111
J Immunol Methods. 2012 Dec 14;386(1-2):112-6
23017277
Immunity. 1999 Dec;11(6):753-61
10626897
J Immunol Methods. 2000 Apr 21;238(1-2):119-31
10758242