Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine.
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.
Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
Kanako L
KL
Lewis
Michele L
ML
Caton
Milena
M
Bogunovic
Melanie
M
Greter
Lucja T
LT
Grajkowska
Dennis
D
Ng
Apostolos
A
Klinakis
Israel F
IF
Charo
Steffen
S
Jung
Jennifer L
JL
Gommerman
Ivaylo I
II
Ivanov
Kang
K
Liu
Miriam
M
Merad
Boris
B
Reizis
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D051883:Receptor, Notch2 / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology* / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D051883:Receptor, Notch2; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3