Origin of the lamina propria dendritic cell network.
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.
Bogunovic
Milena
M
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Ginhoux
Florent
F
Helft
Julie
J
Shang
Limin
L
Hashimoto
Daigo
D
Greter
Melanie
M
Liu
Kang
K
Jakubzick
Claudia
C
Ingersoll
Molly A
MA
Leboeuf
Marylene
M
Stanley
E Richard
ER
Nussenzweig
Michel
M
Lira
Sergio A
SA
Randolph
Gwendalyn J
GJ
Merad
Miriam
M
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D039001:Integrin alpha Chains / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology; D012475:Salmonella / Q000276:immunology / Q000472:pathogenicity; D051941:fms-Like Tyrosine Kinase 3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D039001:Integrin alpha Chains; D019707:Receptors, Chemokine; C091367:alpha E integrins; C497971:Flt3 protein, mouse; D016186:Receptor, Macrophage Colony-Stimulating Factor; D051941:fms-Like Tyrosine Kinase 3