| Literature DB >> 28283063 |
Ai Ing Lim1, Yan Li2, Silvia Lopez-Lastra3, Ralph Stadhouders4, Franziska Paul5, Armanda Casrouge2, Nicolas Serafini2, Anne Puel6, Jacinta Bustamante6, Laura Surace2, Guillemette Masse-Ranson2, Eyal David5, Helene Strick-Marchand2, Lionel Le Bourhis7, Roberto Cocchi8, Davide Topazio8, Paolo Graziano8, Lucia Anna Muscarella8, Lars Rogge9, Xavier Norel10, Jean-Michel Sallenave11, Matthieu Allez12, Thomas Graf4, Rudi W Hendriks13, Jean-Laurent Casanova14, Ido Amit5, Hans Yssel15, James P Di Santo16.
Abstract
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.Entities:
Keywords: cell fate; cytokines; development; humanized mice; innate lymphoid cells; lymphopoiesis; signaling; single cell cloning; transcription factors
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Year: 2017 PMID： 28283063 DOI： 10.1016/j.cell.2017.02.021
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582