Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation

被引：420

作者：

Lim, Ai Ing ^{[1
,2
,3
]}

Li, Yan ^{[1
,2
]}

Lopez-Lastra, Silvia ^{[1
,2
,4
]}

Stadhouders, Ralph ^{[5
]}

Paul, Franziska ^{[6
]}

Casrouge, Armanda ^{[1
,2
]}

Serafini, Nicolas ^{[1
,2
]}

Puel, Anne ^{[7
,8
]}

Bustamante, Jacinta ^{[7
,8
]}

Surace, Laura ^{[1
,2
]}

Masse-Ranson, Guillemette ^{[1
,2
]}

David, Eyal ^{[6
]}

Strick-Marchand, Helene ^{[1
,2
]}

Le Bourhis, Lionel ^{[9
]}

Cocchi, Roberto ^{[10
]}

Topazio, Davide ^{[10
]}

Graziano, Paolo ^{[10
]}

Muscarella, Lucia Anna ^{[10
]}

Rogge, Lars ^{[11
]}

Norel, Xavier ^{[12
]}

Sallenave, Jean-Michel ^{[3
,13
]}

Allez, Matthieu ^{[9
,14
]}

Graf, Thomas ^{[5
]}

Hendriks, Rudi W. ^{[15
]}

Casanova, Jean-Laurent ^{[7
,8
,16
,17
,18
]}

Amit, Ido ^{[6
]}

Yssel, Hans ^{[19
]}

Di Santo, James P. ^{[1
,2
]}

机构：

[1] Inst Pasteur, Innate Immun Unit, F-75724 Paris, France

[2] INSERM, U1223, F-75015 Paris, France

[3] Univ Paris Diderot, Sorbonne Paris Cite, F-75205 Paris, France

[4] Univ Paris 11, Paris Saclay, F-91405 Orsay, France

[5] Barcelona Inst Sci & Technol, Ctr Genom Regulat, Barcelona 08003, Spain

[6] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

[7] INSERM, U1163, Necker Branch, Lab Human Genet Infect Dis, F-75015 Paris, France

[8] Paris Descartes Univ, Imagine Inst, F-75015 Paris, France

[9] Hop St Louis, INSERM, U1160, Inst Univ Hematol, F-75010 Paris, France

[10] Sci Inst Res & Hlth Care Casa Sollievo della Soff, I-71013 San Giovanni Rotondo, Italy

[11] Inst Pasteur, Immunoregulat Unit, F-75724 Paris, France

[12] CHU Xavier Bichat, LVTS, INSERM, U1148, F-75877 Paris, France

[13] Univ Sorbonne Paris Cite, Univ Paris Diderot, Fac Med Site Bichat, INSERM,U1152, F-75018 Paris, France

[14] Hop St Louis, AP HP, Gastroenterol Dept, F-75010 Paris, France

[15] Erasmus MC, Dept Pulm Med, NL-3000 CA Rotterdam, Netherlands

[16] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA

[17] Howard Hughes Med Inst, New York, NY 10065 USA

[18] Necker Hosp Sick Children, Pediat Hematol Immunol Unit, F-75015 Paris, France

[19] Ctr Immunol & Malad Infect, INSERM, U1135, F-75013 Paris, France

来源：

CELL | 2017年 / 168卷 / 06期

基金：

欧盟地平线“2020”;

关键词：

INNATE LYMPHOID-CELLS; HEMATOPOIETIC STEM-CELLS; TRANSCRIPTION FACTOR; FUNCTIONAL PLASTICITY; B-CELL; PROGENITOR; FETAL; EXPRESSION; HOMEOSTASIS; GENERATION;

D O I：

10.1016/j.cell.2017.02.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 forEOMES(+) natural killer (NK) cells, interferon gamma-positive (IFN-gamma(+)) 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.

引用

页码：1086 / +

页数：25

共 48 条

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