@article{4472,
  keywords = {Animals, Mice, Transcription, Genetic, Humans, Cell Differentiation, Cell Lineage, Immunity, Innate, Stem Cells, Lung, Fetus, Liver, Lymphocytes, Interleukin-17, Antigens, CD34, Fetal Blood, Lymphoid Tissue, Proto-Oncogene Proteins c-kit},
  author = {Ai Lim and Yan Li and Silvia Lopez-Lastra and Ralph Stadhouders and Franziska Paul and Armanda Casrouge and Nicolas Serafini and Anne Puel and Jacinta Bustamante and Laura Surace and Guillemette Masse-Ranson and Eyal David and H{\'e}l{\`e}ne Strick-Marchand and Lionel Le Bourhis and Roberto Cocchi and Davide Topazio and Paolo Graziano and Lucia Muscarella and Lars Rogge and Xavier Norel and Jean-Michel Sallenave and Matthieu Allez and Thomas Graf and Rudi Hendriks and Jean-Laurent Casanova and Ido Amit and Hans Yssel and James Di Santo},
  title = {Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation.},
  abstract = { <p>Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T~cells that differentiate from committed ILC precursors (ILCPs). How ILCPs give rise to mature tissue-resident ILCs remains unclear. Here, we identify circulating and tissue ILCPs in humans that fail to express the transcription factors and cytokine outputs of mature ILCs but have these signature loci in an epigenetically poised configuration. Human ILCPs robustly generate all ILC subsets in~vitro and in~vivo. While human ILCPs express low levels of retinoic acid receptor (RAR)-related orphan receptor C (RORC) transcripts, these cells are found in RORC-deficient patients and retain potential for EOMES natural killer (NK) cells, interferon gamma-positive (IFN-γ) ILC1s, interleukin (IL)-13 ILC2s, and for IL-22, but not for IL-17A ILC3s. Our results support a model of tissue ILC differentiation ("ILC-poiesis"), whereby diverse ILC subsets are generated in~situ from systemically distributed ILCPs in response to local environmental signals.</p> },
  year = {2017},
  journal = {Cell},
  volume = {168},
  pages = {1086-1100.e10},
  month = {2017 Mar 09},
  issn = {1097-4172},
  doi = {10.1016/j.cell.2017.02.021},
  language = {eng},
}