PMID- 25411201
OWN - NLM
STAT- MEDLINE
DCOM- 20160226
LR  - 20240210
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 194
IP  - 1
DP  - 2015 Jan 1
TI  - Altered lymph node composition in diphtheria toxin receptor-based mouse models to 
      ablate dendritic cells.
PG  - 307-15
LID - 10.4049/jimmunol.1401999 [doi]
AB  - Dendritic cells (DCs) are key regulators of innate and adaptive immunity. Our 
      understanding of immune function has benefited greatly from mouse models allowing 
      for selective ablation of DCs. Many such models rely on transgenic diphtheria 
      toxin receptor (DTR) expression driven by DC-restricted promoters. This renders 
      DCs sensitive to DT but is otherwise thought to have no effect on immune 
      physiology. In this study, we report that, unexpectedly, mice in which DTR is 
      expressed on conventional DCs display marked lymph node (LN) hypocellularity and 
      reduced frequency of DCs in the same organs but not in spleen or nonlymphoid 
      tissues. Intriguingly, in mixed bone marrow chimeras the phenotype conferred by 
      DTR-expressing DCs is dominant over control bone marrow-derived cells, leading to 
      small LNs and an overall paucity of DCs independently of the genetic ability to 
      express DTR. The finding of alterations in LN composition and size independently 
      of DT challenge suggests that caution must be exercised when interpreting results 
      of experiments obtained with mouse models to inducibly deplete DCs. It further 
      indicates that DTR, a member of the epidermal growth factor family, is 
      biologically active in mice. Its use in cell ablation experiments needs to be 
      considered in light of this activity.
CI  - Copyright (c) 2014 by The American Association of Immunologists, Inc.
FAU - van Blijswijk, Janneke
AU  - van Blijswijk J
AD  - Immunobiology Laboratory, Cancer Research UK, London Research Institute, London 
      WC2A 3LY, United Kingdom.
FAU - Schraml, Barbara U
AU  - Schraml BU
AD  - Immunobiology Laboratory, Cancer Research UK, London Research Institute, London 
      WC2A 3LY, United Kingdom.
FAU - Rogers, Neil C
AU  - Rogers NC
AD  - Immunobiology Laboratory, Cancer Research UK, London Research Institute, London 
      WC2A 3LY, United Kingdom.
FAU - Whitney, Paul G
AU  - Whitney PG
AD  - Immunobiology Laboratory, Cancer Research UK, London Research Institute, London 
      WC2A 3LY, United Kingdom.
FAU - Zelenay, Santiago
AU  - Zelenay S
AD  - Immunobiology Laboratory, Cancer Research UK, London Research Institute, London 
      WC2A 3LY, United Kingdom.
FAU - Acton, Sophie E
AU  - Acton SE
AD  - Immunobiology Laboratory, Cancer Research UK, London Research Institute, London 
      WC2A 3LY, United Kingdom.
FAU - Reis e Sousa, Caetano
AU  - Reis e Sousa C
AD  - Immunobiology Laboratory, Cancer Research UK, London Research Institute, London 
      WC2A 3LY, United Kingdom caetano@cancer.org.uk.
LA  - eng
GR  - 15689/CRUK_/Cancer Research UK/United Kingdom
GR  - A3598/CRUK_/Cancer Research UK/United Kingdom
GR  - WT089009MA/WT_/Wellcome Trust/United Kingdom
GR  - 089009/WT_/Wellcome Trust/United Kingdom
GR  - A15689/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141119
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD11c Antigen)
RN  - 0 (Clec9a protein, mouse)
RN  - 0 (Diphtheria Toxin)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*cytology/immunology
MH  - CD11c Antigen/metabolism
MH  - Dendritic Cells/cytology/*immunology
MH  - Diphtheria Toxin/immunology
MH  - Heparin-binding EGF-like Growth Factor/biosynthesis/*immunology
MH  - Lectins, C-Type/genetics
MH  - Lymph Nodes/cytology/immunology/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Models, Animal
MH  - Receptors, Immunologic/genetics
MH  - Spleen/cytology/immunology
PMC - PMC4272857
MID - EMS60860
OID - NLM: EMS60860
EDAT- 2014/11/21 06:00
MHDA- 2016/02/27 06:00
PMCR- 2015/07/01
CRDT- 2014/11/21 06:00
PHST- 2014/11/21 06:00 [entrez]
PHST- 2014/11/21 06:00 [pubmed]
PHST- 2016/02/27 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - jimmunol.1401999 [pii]
AID - 10.4049/jimmunol.1401999 [doi]
PST - ppublish
SO  - J Immunol. 2015 Jan 1;194(1):307-15. doi: 10.4049/jimmunol.1401999. Epub 2014 Nov 
      19.