Notch2 Receptor Signaling Controls Functional Differentiation of Dendritic Cells in the Spleen and Intestine

SummaryDendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b+ DC subset, Notch signaling blockade ablated a distinct population marked by high expression of the adhesion molecule Esam. The Notch-dependent Esamhi DC subset required lymphotoxin beta receptor signaling, proliferated in situ, and facilitated CD4+ T cell priming. The Notch-independent Esamlo DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b+CD103+ DCs in the intestinal lamina propria and to a corresponding decrease of IL-17-producing CD4+ T cells in the intestine. Thus, Notch2 is a common differentiation signal for T cell-priming CD11b+ DC subsets in the spleen and intestine.

Graphical AbstractFigure optionsDownload high-quality image (249 K)Download as PowerPoint slideHighlights
► Notch2 controls differentiation of splenic classical DCs
► Notch2 dependence defines a distinct Esamhi population of splenic CD11b+ DCs
► The Esamhi CD11b+ DCs are required for CD4+ T cell priming in the spleen
► Notch2 controls differentiation of CD11b+CD103+ DCs in the intestinal lamina propria