Dendritic 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 Esam hi DC subset required lymphotoxin beta receptor signaling, proliferated in situ, and facilitated CD4 + T cell priming. The Notch-independent Esam lo 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.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Infectious Diseases