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 CD8α. Here we describe a subset of CD8α⁺ DC in lymphoid organs of naïve mice characterized by expression of the CX3CR1 chemokine receptor. CX ₃CR1⁺ CD8α⁺ DC lack hallmarks of classical CD8α⁺ 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 ⁺ CD8α⁺ DC resemble CD8α^- cDC. The microarray analysis further revealed a unique plasmacytoid DC (PDC) gene signature of CX₃CR1⁺ CD8α⁺ 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 CX ₃CR1⁺ CD8α⁺ DC requires E2-2, the critical transcriptional regulator of PDC. Thus, CX₃CR1⁺ CD8α⁺ 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 CD8α⁺ and CD8α^- DC, and should assist the identification of human counterparts of murine DC subsets.