Peripheral CD103⁺ dendritic cells form a unified subset developmentally related to CD8α⁺ conventional dendritic cells

Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8α⁺ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3^-/- mice also lack CD103⁺CD11b ^- DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3^-/- mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103⁺CD11b^- DCs, with the population of CD103⁺CD11b⁺ DCs remaining intact. Batf3^-/- mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103⁺ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8α⁺ cDCs and nonlymphoid CD103⁺ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ-resident CD8α⁺ cDCs and nonlymphoid CD103⁺ DCs.