The origin and development of nonlymphoid tissue CD103+ DCs

• Published in: The Journal of experimental medicine Vol. 206; no. 13; pp. 3115 - 3130
• Main Authors: Ginhoux, Florent, Liu, Kang, Helft, Julie, Bogunovic, Milena, Greter, Melanie, Hashimoto, Daigo, Price, Jeremy, Yin, Na, Bromberg, Jonathan, Lira, Sergio A., Stanley, E. Richard, Nussenzweig, Michel, Merad, Miriam
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 21.12.2009
• Subjects: Animals; Antigens, CD - analysis; CD11b Antigen - analysis; CD8 Antigens - analysis; Cell Differentiation; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - physiology; fms-Like Tyrosine Kinase 3 - analysis; fms-Like Tyrosine Kinase 3 - physiology; Homeostasis; Inhibitor of Differentiation Protein 2 - physiology; Integrin alpha Chains - analysis; Interferon Regulatory Factors - physiology; Male; Mice; Mice, Inbred C57BL; Receptor, Macrophage Colony-Stimulating Factor - analysis; Receptor, Macrophage Colony-Stimulating Factor - physiology; Stem Cells - physiology
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20091756

CD103+ dendritic cells (DCs) in nonlymphoid tissues are specialized in the cross-presentation of cell-associated antigens. However, little is known about the mechanisms that regulate the development of these cells. We show that two populations of CD11c+MHCII+ cells separated on the basis of CD103 and CD11b expression coexist in most nonlymphoid tissues with the exception of the lamina propria. CD103+ DCs are related to lymphoid organ CD8+ DCs in that they are derived exclusively from pre-DCs under the control of fms-like tyrosine kinase 3 (Flt3) ligand, inhibitor of DNA protein 2 (Id2), and IFN regulatory protein 8 (IRF8). In contrast, lamina propria CD103+ DCs express CD11b and develop independently of Id2 and IRF8. The other population of CD11c+MHCII+ cells in tissues, which is CD103−CD11b+, is heterogenous and depends on both Flt3 and MCSF-R. Our results reveal that nonlymphoid tissue CD103+ DCs and lymphoid organ CD8+ DCs derive from the same precursor and follow a related differentiation program.