Identification and distribution of developing innate lymphoid cells in the fetal mouse intestine

Nat Immunol. 2015 Feb;16(2):153-60. doi: 10.1038/ni.3057. Epub 2014 Dec 15.


Fetal lymphoid tissue inducer (LTi) cells are required for lymph node and Peyer's patch (PP) organogenesis, but where these specialized group 3 innate lymphoid cells (ILC3s) develop remains unclear. Here, we identify extrahepatic arginase-1(+) Id2(+) fetal ILC precursors that express a transitional developmental phenotype (ftILCPs) and differentiate into ILC1s, ILC2s and ILC3s in vitro. These cells populate the intestine by embryonic day (E) 13.5 and, before PP organogenesis (E14.5-15), are broadly dispersed in the proximal gut, correlating with regions where PPs first develop. At E16.5, after PP development begins, ftILCPs accumulate at PP anlagen in a lymphotoxin-α-dependent manner. Thus, ftILCPs reside in the intestine during PP development, where they aggregate at PP anlagen after stromal cell activation and become a localized source of ILC populations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginase / metabolism
  • Cell Differentiation*
  • Cells, Cultured
  • Fetus / cytology
  • Fetus / immunology
  • Flow Cytometry
  • Immunity, Innate*
  • Immunohistochemistry
  • Intestine, Small / cytology*
  • Intestine, Small / embryology*
  • Intestine, Small / immunology
  • Lymphoid Tissue / cytology*
  • Lymphoid Tissue / embryology*
  • Lymphoid Tissue / immunology
  • Mice


  • Arg1 protein, mouse
  • Arginase