Origin of the Lamina Propria Dendritic Cell Network

• Published in: Immunity (Cambridge, Mass.) Vol. 31; no. 3; pp. 513 - 525
• Main Authors: Bogunovic, Milena, 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.09.2009; Elsevier Limited; Elsevier
• Subjects: Animals; Antigens, CD; Antigens, CD - immunology; Bacteria; Cell Differentiation; Cell Lineage; Cell Movement; CELLIMMUNO; CX3C Chemokine Receptor 1; Dendritic Cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Flow cytometry; fms-Like Tyrosine Kinase 3; fms-Like Tyrosine Kinase 3 - deficiency; fms-Like Tyrosine Kinase 3 - genetics; fms-Like Tyrosine Kinase 3 - immunology; Genotype & phenotype; Grants; Homeostasis; Hypotheses; Immunology; Integrin alpha Chains; Integrin alpha Chains - immunology; Intestinal Mucosa; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Life Sciences; Lymph Nodes; Lymph Nodes - immunology; Mice; Mice, Knockout; MOLIMMUNO; Phenotype; Receptor, Macrophage Colony-Stimulating Factor; Receptor, Macrophage Colony-Stimulating Factor - immunology; Receptors, Chemokine; Receptors, Chemokine - immunology; Salmonella; Salmonella - immunology; Salmonella - pathogenicity; Small intestine; Studies; MOLIMMUNO; CELLIMMUNO
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2009.08.010

CX 3CR1 + 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 3CR1 + 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 3CR1 − lamina propria DCs under the control of Flt3 and granulocyte-macrophage-colony-stimulating factor receptor (GM-CSFR) ligands. CD103 +CX 3CR1 − DCs but not CD103 −CX 3CR1 + 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.