Immunity
Volume 35, Issue 5, 23 November 2011, Pages 780-791
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Article
Notch2 Receptor Signaling Controls Functional Differentiation of Dendritic Cells in the Spleen and Intestine

https://doi.org/10.1016/j.immuni.2011.08.013Get rights and content
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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.

Highlights

► 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

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