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PMID: 19733489 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Origin of the lamina propria dendritic cell network.

Immunity ·Vol. 31 ·No. 3 ·2009-09-18 ·Pages 513-25

Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, Greter M, Liu K, Jakubzick C, Ingersoll MA, Leboeuf M, Stanley ER, Nussenzweig M, Lira SA, Randolph GJ, Merad M

Abstract

CX(3)CR1(+) and CD103(+) dendritic cells (DCs) in intestinal lamina propria play a key role in mucosal immunity. However, the origin and the developmental pathways that regulate their differentiation in the lamina propria remain unclear. We showed that monocytes gave rise exclusively to CD103(-)CX(3)CR1(+) lamina propria DCs under the control of macrophage-colony-stimulating factor receptor (M-CSFR) and Fms-like thyrosine kinase 3 (Flt3) ligands. In contrast, common DC progenitors (CDP) and pre-DCs, which give rise to lymphoid organ DCs but not to monocytes, differentiated exclusively into CD103(+)CX(3)CR1(-) lamina propria DCs under the control of Flt3 and granulocyte-macrophage-colony-stimulating factor receptor (GM-CSFR) ligands. CD103(+)CX(3)CR1(-) DCs but not CD103(-)CX(3)CR1(+) DCs in the lamina propria constitutively expressed CCR7 and were the first DCs to transport pathogenic Salmonella from the intestinal tract to the mesenteric lymph nodes. Altogether, these results underline the diverse origin of the lamina propria DC network and identify mucosal DCs that arise from pre-DCs as key sentinels of the gut immune system.

MeSH Terms
Animals Antigens, CD/immunology CX3C Chemokine Receptor 1 Cell Differentiation Cell Lineage Cell Movement Dendritic Cells/cytology,immunology Integrin alpha Chains/immunology Intestinal Mucosa/cytology,immunology Lymph Nodes/immunology Mice Mice, Knockout Phenotype Receptor, Macrophage Colony-Stimulating Factor/immunology Receptors, Chemokine/immunology Salmonella/immunology,pathogenicity fms-Like Tyrosine Kinase 3/deficiency,genetics,immunology
Chemicals
Antigens, CD CX3C Chemokine Receptor 1 Cx3cr1 protein, mouse Integrin alpha Chains Receptors, Chemokine alpha E integrins Flt3 protein, mouse Receptor, Macrophage Colony-Stimulating Factor fms-Like Tyrosine Kinase 3
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Bogunovic Milena
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Ginhoux Florent
Helft Julie
Shang Limin
Hashimoto Daigo
Greter Melanie
Liu Kang
Jakubzick Claudia
Ingersoll Molly A
Leboeuf Marylene
Stanley E Richard
Nussenzweig Michel
Lira Sergio A
Randolph Gwendalyn J
Merad Miriam
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2009.08.010
Published
2009-09-18
Epub
2009-00-10
Pages
513-25
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2778256
Subset
IM
Grants
NHLBI NIH HHS · R01 HL086899 · United States
NIAID NIH HHS · AI49653 · United States
NCI NIH HHS · CA112100 · United States
NIDDK NIH HHS · P01 DK072201 · United States
NCI NIH HHS · CA086899 · United States
NHLBI NIH HHS · R01 HL086899-01 · United States
NCI NIH HHS · CA32551 · United States
NCI NIH HHS · CA26504 · United States
Corrections
CommentIn
PMID: 19766089
External Links
PubMed source DOI: 10.1016/j.immuni.2009.08.010 PMC Full Text View journal details
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