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; 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; 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, 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, James P. Di Santo

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

407 Scopus citations

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 (US)
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 - Mar 9 2017
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

Keywords

cell fate
cytokines
development
humanized mice
innate lymphoid cells
lymphopoiesis
signaling
single cell cloning
transcription factors

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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, L., Cocchi, R., Topazio, D., Graziano, P., Muscarella, L. A., Rogge, L., ... Di Santo, 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{de04a2926935488a82e6bc7928738ab8,

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.",

keywords = "cell fate, cytokines, development, humanized mice, innate lymphoid cells, lymphopoiesis, signaling, single cell cloning, transcription factors",

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}, Lionel and Roberto Cocchi and Davide Topazio and Paolo Graziano and Muscarella, {Lucia Anna} and Lars Rogge and Xavier Norel and Sallenave, {Jean Michel} and Matthieu Allez and Thomas Graf and Hendriks, {Rudi W.} and Casanova, {Jean Laurent} and Ido Amit and Hans Yssel and {Di 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 = "English (US)",

volume = "168",

pages = "1086--1100.e10",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "6",

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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, L, Cocchi, R, Topazio, D, Graziano, P, Muscarella, LA, Rogge, L, Norel, X, Sallenave, JM, Allez, M, Graf, T, Hendriks, RW, Casanova, JL, Amit, I, Yssel, H & Di Santo, JP 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, 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, 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.

KW - cell fate

KW - cytokines

KW - development

KW - humanized mice

KW - innate lymphoid cells

KW - lymphopoiesis

KW - signaling

KW - single cell cloning

KW - transcription factors

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

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

U2 - 10.1016/j.cell.2017.02.021

DO - 10.1016/j.cell.2017.02.021

M3 - Article

C2 - 28283063

AN - SCOPUS:85014819484

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

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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