期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：16
页码：5986-5991
DOI：10.1073/pnas.1401671111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 CD11clowCX3CR1+ cells. The CD11clowCX3CR1+ cells could not differentiate to CD11c+CX3CR1+ cells, suggesting that CD11clowCX3CR1+ 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.
