[PDF][PDF] Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine

KL Lewis, ML Caton, M Bogunovic, M Greter… - Immunity, 2011 - cell.com
KL Lewis, ML Caton, M Bogunovic, M Greter, LT Grajkowska, D Ng, A Klinakis, IF Charo…
Immunity, 2011cell.com
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 …
Summary
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 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.
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