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DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and nonlymphoid tissues

Poulin, Lionel F.; Reyal, Yasmin; Uronen-Hansson, Heli LU ; Schraml, Barbara U.; Sancho, David; Murphy, Kenneth M.; Håkansson, Ulf LU ; Moita, Luis Ferreira; Agace, William LU and Bonnet, Dominique, et al. (2012) In Blood 119(25). p.6052-6062
Abstract
Mouse CD8 alpha(+) dendritic cells (DCs) in lymphoid organs and CD103(+) CD11b(-) DCs in nonlymphoid tissues share phenotypic and functional similarities, as well as a unique shared developmental dependence on the transcription factor Batf3. Human DCs resembling mouse CD8 alpha(+) DCs in phenotype and function have been identified in human blood, spleen, and tonsil. However, it is not clear whether such cells are also present in human nonlymphoid organs, and their equivalence to mouse CD8 alpha(+) DC has recently b een questioned. Furthermore, the identification of "CD8 alpha(+) DC-like" cells across different tissues and species remains problematic because of the lack of a unique marker that can be used to unambiguously define lineage... (More)
Mouse CD8 alpha(+) dendritic cells (DCs) in lymphoid organs and CD103(+) CD11b(-) DCs in nonlymphoid tissues share phenotypic and functional similarities, as well as a unique shared developmental dependence on the transcription factor Batf3. Human DCs resembling mouse CD8 alpha(+) DCs in phenotype and function have been identified in human blood, spleen, and tonsil. However, it is not clear whether such cells are also present in human nonlymphoid organs, and their equivalence to mouse CD8 alpha(+) DC has recently b een questioned. Furthermore, the identification of "CD8 alpha(+) DC-like" cells across different tissues and species remains problematic because of the lack of a unique marker that can be used to unambiguously define lineage members. Here we show that mouse CD8 alpha(+) DCs and CD103(+) CD11b(-) DCs can be defined by shared high expression of DNGR-1 (CLEC9A). We further show that DNGR-1 uniquely marks a CD11b(-) human DC population present in both lymphoid and nonlymphoid tissues of humans and humanized mice. Finally, we demonstrate that knockdown of Batf3 selectively prevents the development of DNGR-1(+) human DCs in vitro. Thus, high expression of DNGR-1 specifically and universally identifies a unique DC subset in mouse and humans. Evolutionarily conserved Batf3 dependence justifies classification of DNGR-1(hi) DCs as a distinct DC lineage. (Blood. 2012; 119(25): 6052-6062) (Less)
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Contribution to journal
publication status
published
subject
in
Blood
volume
119
issue
25
pages
6052 - 6062
publisher
American Society of Hematology
external identifiers
  • wos:000307398700020
  • scopus:84860240081
ISSN
1528-0020
DOI
10.1182/blood-2012-01-406967
language
English
LU publication?
yes
id
3e81de8a-8448-44a9-b750-162bb88d0566 (old id 3073377)
date added to LUP
2012-10-05 07:13:24
date last changed
2017-10-22 03:12:57
@article{3e81de8a-8448-44a9-b750-162bb88d0566,
  abstract     = {Mouse CD8 alpha(+) dendritic cells (DCs) in lymphoid organs and CD103(+) CD11b(-) DCs in nonlymphoid tissues share phenotypic and functional similarities, as well as a unique shared developmental dependence on the transcription factor Batf3. Human DCs resembling mouse CD8 alpha(+) DCs in phenotype and function have been identified in human blood, spleen, and tonsil. However, it is not clear whether such cells are also present in human nonlymphoid organs, and their equivalence to mouse CD8 alpha(+) DC has recently b een questioned. Furthermore, the identification of "CD8 alpha(+) DC-like" cells across different tissues and species remains problematic because of the lack of a unique marker that can be used to unambiguously define lineage members. Here we show that mouse CD8 alpha(+) DCs and CD103(+) CD11b(-) DCs can be defined by shared high expression of DNGR-1 (CLEC9A). We further show that DNGR-1 uniquely marks a CD11b(-) human DC population present in both lymphoid and nonlymphoid tissues of humans and humanized mice. Finally, we demonstrate that knockdown of Batf3 selectively prevents the development of DNGR-1(+) human DCs in vitro. Thus, high expression of DNGR-1 specifically and universally identifies a unique DC subset in mouse and humans. Evolutionarily conserved Batf3 dependence justifies classification of DNGR-1(hi) DCs as a distinct DC lineage. (Blood. 2012; 119(25): 6052-6062)},
  author       = {Poulin, Lionel F. and Reyal, Yasmin and Uronen-Hansson, Heli and Schraml, Barbara U. and Sancho, David and Murphy, Kenneth M. and Håkansson, Ulf and Moita, Luis Ferreira and Agace, William and Bonnet, Dominique and Reis e Sousa, Caetano},
  issn         = {1528-0020},
  language     = {eng},
  number       = {25},
  pages        = {6052--6062},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and nonlymphoid tissues},
  url          = {http://dx.doi.org/10.1182/blood-2012-01-406967},
  volume       = {119},
  year         = {2012},
}