Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine.
Immunity, 2011/11/23;35(5):780-91.
Lewis KL[1], Caton ML, Bogunovic M, Greter M, Grajkowska LT, Ng D, Klinakis A, Charo IF, Jung S, Gommerman JL, Ivanov II, Liu K, Merad M, Reizis B
Affiliations
PMID: 22018469DOI: 10.1016/j.immuni.2011.08.013
Impact factor: 43.474
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.
MeSH terms
Animals; Cell Differentiation; Cells, Cultured; Dendritic Cells; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Immunoglobulin J Recombination Signal Sequence-Binding Protein; Intestinal Mucosa; Intestines; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Phenotype; Receptor, Notch2; Signal Transduction; Spleen; fms-Like Tyrosine Kinase 3
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