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

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

Research output: Contribution to journalArticlepeer-review

288 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)780-791
Number of pages12
JournalImmunity
Volume35
Issue number5
DOIs
StatePublished - Nov 23 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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