Abstract
Batf3 is a transcription factor that impacts the development of CD103+ tissue-resident dendritic cells (DCs). However, whether Batf3 is absolutely required for the development of CD8+ DCs remains controversial. Id2 is required for CD8+ DC development. Here we show that bone marrow chimeric mice with a deletion of Id2 in the CD11c compartment lose the ability to reject a skin graft expressing a non-self protein antigen or mount a delayed hypersensitivity response. In contrast, Batf3-/- mice remained competent for skin graft rejection and delayed hypersensitivity, and retained a CD8+ DC population with markers characteristic of the CD11b+ DC lineage, including CD11b, CD4 and CD172α, as well as the key regulator transcription factor IRF4, but lacked IRF8 expression. CD8+ DCs in Batf3-/- mice took up and cleaved protein antigen and larger particles but were unable to phagocytose dying cells, a characteristic feature to the CD8+ DC lineage. These data clarify a requirement for CD8+ lineage DCs to induce effectors of neo-antigen-driven skin graft rejection, and improve our understanding of DC subtype commitment by demonstrating that in the absence of Batf3 CD8+ DCs can change their fate and become CD11b+ DCs.