Differentiation of CD11c+ CX3CR1+ cells in the small intestine requires Notch signaling.
The gastrointestinal tract comes into direct contact with environmental agents, including bacteria, viruses, and foods. Intestine-specific subsets of immune cells maintain gut homeostasis by continuously sampling luminal antigens and maintaining immune tolerance. CD11c(+)CX3CR1(+) cells sample luminal antigens in the small intestine and contribute to the trafficking of bacteria to lymph nodes under dysbiotic conditions. The molecular mechanisms crucial for the differentiation of CD11c(+)CX3CR1(+) cells remain unclear. Here we demonstrate that the Notch1- or Notch2-Rbpj axis is essential for the development of CD11c(+)CX3CR1(+) cells. In mice in which Rbpj or Notch1 and Notch2 were deleted from CD11c(+) cells, there was a deficit of CD11c(+)CX3CR1(+) cells and an accumulation of CD11c(low)CX3CR1(+) cells. The CD11c(low)CX3CR1(+) cells could not differentiate to CD11c(+)CX3CR1(+) cells, suggesting that CD11c(low)CX3CR1(+) cells represent a lineage distinct from CD11c(+)CX3CR1(+) cells. These data indicate that Notch signaling is essential for lineage fixation of intestinal CD11c(+)CX3CR1(+) cells.
Department of Immunology and Parasitology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Chieko
C
Ishifune
Satoshi
S
Maruyama
Yuki
Y
Sasaki
Hideo
H
Yagita
Katsuto
K
Hozumi
Taisuke
T
Tomita
Kenji
K
Kishihara
Koji
K
Yasutomo
D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D002452:Cell Count; D002454:Cell Differentiation; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000172:deficiency / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019707:Receptors, Chemokine / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
D039521:CD11c Antigen; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D019707:Receptors, Chemokine; D051880:Receptors, Notch