CX3CR1+ CD8α+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells

Lymphoid organs are characterized by a complex network of phenotypically distinct dendritic cells (DC) with potentially unique roles in pathogen recognition and immunostimulation. Classical DC (cDC) include two major subsets distinguished in the mouse by the expression of CD8 alpha. Here we describe a subset of CD8 alpha(+) DC in lymphoid organs of na ve mice characterized by expression of the CX3CR1 chemokine receptor. CX3CR1(+) CD8 alpha(+) DC lack hallmarks of classical CD8 alpha(+) DC, including IL-12 secretion, the capacity to crosspresent antigen, and their developmental dependence on the transcriptional factor BatF3. Gene-expression profiling showed that CX3CR1(+) CD8 alpha(+) DC resemble CD8 alpha-cDC. The microarray analysis further revealed a unique plasmacytoid DC (PDC) gene signature of CX3CR1(+) CD8 alpha(+) DC. A PDC relationship of the cells is supported further by the fact that they harbor characteristic D-J Ig gene rearrangements and that development of CX3CR1(+) CD8 alpha(+) DC requires E2-2, the critical transcriptional regulator of PDC. Thus, CX3CR1(+) CD8 alpha(+) DC represent a unique DC subset, related to but distinct from PDC. Collectively, the expression-profiling data of this study refine the resolution of previous DC definitions, sharpen the border of classical CD8 alpha(+) and CD8 alpha(-) DC, and should assist the identification of human counterparts of murine DC subsets.