The origin and development of nonlymphoid tissue CD103+ DCs.
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.
Ginhoux
Florent
F
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Liu
Kang
K
Helft
Julie
J
Bogunovic
Milena
M
Greter
Melanie
M
Hashimoto
Daigo
D
Price
Jeremy
J
Yin
Na
N
Bromberg
Jonathan
J
Lira
Sergio A
SA
Stanley
E Richard
ER
Nussenzweig
Michel
M
Merad
Miriam
M
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D039481:CD11b Antigen / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D006706:Homeostasis; D051797:Inhibitor of Differentiation Protein 2 / Q000502:physiology; D039001:Integrin alpha Chains / Q000032:analysis*; D050835:Interferon Regulatory Factors / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D051941:fms-Like Tyrosine Kinase 3 / Q000032:analysis / Q000502:physiology; D000099185:Interferon Regulatory Factor-8
D015703:Antigens, CD; D039481:CD11b Antigen; D016827:CD8 Antigens; D051797:Inhibitor of Differentiation Protein 2; D039001:Integrin alpha Chains; D050835:Interferon Regulatory Factors; D016186:Receptor, Macrophage Colony-Stimulating Factor; D051941:fms-Like Tyrosine Kinase 3; D000099185:Interferon Regulatory Factor-8; C497452:Idb2 protein, mouse; C091367:alpha E integrins; C497971:Flt3 protein, mouse