Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation.

TitleSystemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation.
Publication TypeJournal Article
Year of Publication2017
AuthorsLim, AIng, Li, Y, Lopez-Lastra, S, Stadhouders, R, Paul, F, Casrouge, A, Serafini, N, Puel, A, Bustamante, J, Surace, L, Masse-Ranson, G, David, E, Strick-Marchand, H, Le Bourhis, L, Cocchi, R, Topazio, D, Graziano, P, Muscarella, LAnna, Rogge, L, Norel, X, Sallenave, J-M, Allez, M, Graf, T, Hendriks, RW, Casanova, J-L, Amit, I, Yssel, H, Di Santo, JP
JournalCell
Volume168
Issue6
Pagination1086-1100.e10
Date Published2017/03/09
ISSN1097-4172
KeywordsAnimals, Antigens, CD34, Cell Differentiation, Cell Lineage, Fetal Blood, Fetus, Humans, Immunity, Innate, Interleukin-17, Liver, Lung, Lymphocytes, Lymphoid Tissue, Mice, Proto-Oncogene Proteins c-kit, Stem Cells, Transcription, Genetic
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.

DOI10.1016/j.cell.2017.02.021
Alternate JournalCell
PubMed ID28283063