Kanako L Lewis,
Michele L Caton,
Milena Bogunovic,
Melanie Greter, Lucja T Grajkowska,
Dennis Ng,
Apostolos Klinakis,
Israel F Charo,
Steffen Jung,
Jennifer L Gommerman,
Ivaylo I Ivanov,
Kang Liu,
Miriam Merad,
Boris Reizis
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ABSTRACT: 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.
Immunity 11/2011; 35(5):780-91. · 21.64 Impact Factor
