Differentiation of CD11c+CX3CR1+ cells in the small intestine requires Notch signaling

Abstract

The gastrointestinal tract comes into direct contact with environmental agents, including bacteria, viruses, and foods. Intestinespecific 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+CX 3CR1+ 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 CD11clowCX3CR1+ cells. The CD11c lowCX3CR1+ cells could not differentiate to CD11c+CX3CR1+ cells, suggesting that CD11c lowCX3CR1+ 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.