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.