CCR2+CD103− intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells

C. L. Scott; C. C. Bain; P. B. Wright; D. Sichien; K. Kotarsky; E. K. Persson; K. Luda; M. Guilliams; B. N. Lambrecht; William Winston Agace; S. WF Milling; A. M. Mowat

doi:10.1038/mi.2014.70

CCR2⁺CD103⁻ intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells

C. L. Scott
, C. C. Bain
, P. B. Wright
, D. Sichien
, K. Kotarsky
, E. K. Persson
, K. Luda
, M. Guilliams
, B. N. Lambrecht
, William Winston Agace
, S. WF Milling
, A. M. Mowat

Lund University
University of Glasgow
Ghent University

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter of intense debate. Although CD103⁺ mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103- MPs remain controversial. We show here that intestinal CD103^-CD11b⁺MPs can be separated clearly into DCs and mφs based on phenotype, gene profile, and kinetics. CD64^-CD103^-CD11b⁺ MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6Chi monocytes. Surprisingly, a significant proportion of these CD103^-CD11b⁺ DCs express CCR2 and there is a selective decrease in CD103^-CD11b⁺ DCs in mice lacking this chemokine receptor. CCR2⁺CD103^- DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2⁺ DCs that is involved in priming mucosal T helper type 17 (Th17) responses.

Original language	English
Journal	Mucosal Immunology
Volume	8
Issue number	2
Pages (from-to)	327-339
ISSN	1933-0219
DOIs	https://doi.org/10.1038/mi.2014.70
Publication status	Published - 2015
Externally published	Yes

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This work is licensed under the CreativeCommons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-sa/3.0/

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Scott, C. L., Bain, C. C., Wright, P. B., Sichien, D., Kotarsky, K., Persson, E. K., Luda, K., Guilliams, M., Lambrecht, B. N., Agace, W. W., Milling, S. WF., & Mowat, A. M. (2015). CCR2⁺CD103⁻ intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells. Mucosal Immunology, 8(2), 327-339. https://doi.org/10.1038/mi.2014.70

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title = "CCR2+CD103− intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells",

abstract = "The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter of intense debate. Although CD103+ mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103- MPs remain controversial. We show here that intestinal CD103-CD11b+ MPs can be separated clearly into DCs and mφs based on phenotype, gene profile, and kinetics. CD64-CD103-CD11b+ MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6Chi monocytes. Surprisingly, a significant proportion of these CD103-CD11b+ DCs express CCR2 and there is a selective decrease in CD103-CD11b+ DCs in mice lacking this chemokine receptor. CCR2+CD103- DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2+ DCs that is involved in priming mucosal T helper type 17 (Th17) responses.",

author = "Scott, \{C. L.\} and Bain, \{C. C.\} and Wright, \{P. B.\} and D. Sichien and K. Kotarsky and Persson, \{E. K.\} and K. Luda and M. Guilliams and Lambrecht, \{B. N.\} and Agace, \{William Winston\} and Milling, \{S. WF\} and Mowat, \{A. M.\}",

note = "This work is licensed under the CreativeCommons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-sa/3.0/",

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T1 - CCR2+CD103− intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells

AU - Scott, C. L.

AU - Bain, C. C.

AU - Wright, P. B.

AU - Sichien, D.

AU - Kotarsky, K.

AU - Persson, E. K.

AU - Luda, K.

AU - Guilliams, M.

AU - Lambrecht, B. N.

AU - Agace, William Winston

AU - Milling, S. WF

AU - Mowat, A. M.

N1 - This work is licensed under the CreativeCommons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-sa/3.0/

PY - 2015

Y1 - 2015

N2 - The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter of intense debate. Although CD103+ mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103- MPs remain controversial. We show here that intestinal CD103-CD11b+ MPs can be separated clearly into DCs and mφs based on phenotype, gene profile, and kinetics. CD64-CD103-CD11b+ MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6Chi monocytes. Surprisingly, a significant proportion of these CD103-CD11b+ DCs express CCR2 and there is a selective decrease in CD103-CD11b+ DCs in mice lacking this chemokine receptor. CCR2+CD103- DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2+ DCs that is involved in priming mucosal T helper type 17 (Th17) responses.

AB - The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter of intense debate. Although CD103+ mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103- MPs remain controversial. We show here that intestinal CD103-CD11b+ MPs can be separated clearly into DCs and mφs based on phenotype, gene profile, and kinetics. CD64-CD103-CD11b+ MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6Chi monocytes. Surprisingly, a significant proportion of these CD103-CD11b+ DCs express CCR2 and there is a selective decrease in CD103-CD11b+ DCs in mice lacking this chemokine receptor. CCR2+CD103- DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2+ DCs that is involved in priming mucosal T helper type 17 (Th17) responses.

U2 - 10.1038/mi.2014.70

DO - 10.1038/mi.2014.70

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