Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation

Ai Ing Lim; Yan Li; Silvia Lopez-Lastra; Ralph Stadhouders; Franziska Paul; Armanda Casrouge; Nicolas Serafini; Anne Puel; Jacinta Bustamante; Laura Surace; Guillemette Masse-Ranson; Eyal David; Helene Strick-Marchand; Bourhis, Lionel Le Bourhis; Roberto Cocchi; Davide Topazio; Paolo Graziano; Lucia Anna Muscarella; Lars Rogge; Xavier Norel; Jean-Michel Sallenave; Matthieu Allez; Thomas Graf; Rudi W. Hendriks; Jean-Laurent Casanova; Ido Amit; Hans Yssel; Santo, James P. Di Santo

doi:10.1016/j.cell.2017.02.021

Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation

Ai Ing Lim, Yan Li, Silvia Lopez-Lastra, Ralph Stadhouders, Franziska Paul, Armanda Casrouge, Nicolas Serafini, Anne Puel, Jacinta Bustamante, Laura Surace, Guillemette Masse-Ranson, Eyal David, Helene Strick-Marchand, Bourhis, Lionel Le Bourhis, Roberto Cocchi, Davide Topazio, Paolo Graziano, Lucia Anna Muscarella, Lars Rogge, Xavier NorelJean-Michel Sallenave, Matthieu Allez, Thomas Graf, Rudi W. Hendriks, Jean-Laurent Casanova, Ido Amit, Hans Yssel, Santo, James P. Di Santo

Department of Systems Immunology

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1086-1100.e10
Journal	Cell
Volume	168
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2017.02.021
State	Published - 9 Mar 2017

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.cell.2017.02.021

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Lim, A. I., 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, B. L., Cocchi, R., Topazio, D., Graziano, P., Muscarella, L. A., Rogge, L., ... Di Santo, S. J. P. (2017). Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation. Cell, 168(6), 1086-1100.e10. https://doi.org/10.1016/j.cell.2017.02.021

@article{f7754fa5f961428782b0457042392a06,

title = "Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation",

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.",

author = "Lim, \{Ai Ing\} 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 Helene Strick-Marchand and \{Le Bourhis\}, \{Bourhis, Lionel\} and Roberto Cocchi and Davide Topazio and Paolo Graziano and Muscarella, \{Lucia Anna\} and Lars Rogge and Xavier Norel and Jean-Michel Sallenave and Matthieu Allez and Thomas Graf and Hendriks, \{Rudi W.\} and Jean-Laurent Casanova and Ido Amit and Hans Yssel and \{Di Santo\}, \{Santo, James P.\}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = mar,

day = "9",

doi = "10.1016/j.cell.2017.02.021",

language = "الإنجليزيّة",

volume = "168",

pages = "1086--1100.e10",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "6",

}

Lim, AI, 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, BL, Cocchi, R, Topazio, D, Graziano, P, Muscarella, LA, Rogge, L, Norel, X, Sallenave, J-M, Allez, M, Graf, T, Hendriks, RW, Casanova, J-L, Amit, I, Yssel, H & Di Santo, SJP 2017, 'Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation', Cell, vol. 168, no. 6, pp. 1086-1100.e10. https://doi.org/10.1016/j.cell.2017.02.021

TY - JOUR

T1 - Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation

AU - Lim, Ai Ing

AU - Li, Yan

AU - Lopez-Lastra, Silvia

AU - Stadhouders, Ralph

AU - Paul, Franziska

AU - Casrouge, Armanda

AU - Serafini, Nicolas

AU - Puel, Anne

AU - Bustamante, Jacinta

AU - Surace, Laura

AU - Masse-Ranson, Guillemette

AU - David, Eyal

AU - Strick-Marchand, Helene

AU - Le Bourhis, Bourhis, Lionel

AU - Cocchi, Roberto

AU - Topazio, Davide

AU - Graziano, Paolo

AU - Muscarella, Lucia Anna

AU - Rogge, Lars

AU - Norel, Xavier

AU - Sallenave, Jean-Michel

AU - Allez, Matthieu

AU - Graf, Thomas

AU - Hendriks, Rudi W.

AU - Casanova, Jean-Laurent

AU - Amit, Ido

AU - Yssel, Hans

AU - Di Santo, Santo, James P.

PY - 2017/3/9

Y1 - 2017/3/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85014819484&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2017.02.021

DO - 10.1016/j.cell.2017.02.021

M3 - مقالة

SN - 0092-8674

VL - 168

SP - 1086-1100.e10

JO - Cell

JF - Cell

IS - 6

ER -

Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation

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