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

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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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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.",

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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/

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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.

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