Co-option of Neutrophil Fates by Tissue Environments

被引：322

作者：

Ballesteros, Ivan ^{[1
]}

Rubio-Ponce, Andrea ^{[1
,2
]}

Genua, Marco ^{[3
,4
]}

Lusito, Eleonora ^{[3
,4
]}

Kwok, Immanuel ^{[5
]}

Fernandez-Calvo, Gabriel ^{[6
,7
]}

Khoyratty, Tariq E. ^{[8
]}

van Grinsven, Erinke ^{[8
]}

Gonzalez-Hernandez, Sara ^{[1
]}

Angel Nicolas-Avila, Jose ^{[1
]}

Vicanolo, Tommaso ^{[1
]}

Maccataio, Antonio ^{[1
]}

Benguria, Alberto ^{[9
]}

Li, Jackson LiangYao ^{[1
,5
]}

Adrover, Jose M. ^{[1
]}

Aroca-Crevillen, Alejandra ^{[1
]}

Quintana, Juan A. ^{[1
]}

Martin-Salamanca, Sandra ^{[1
]}

Mayo, Francisco ^{[1
]}

Ascher, Stefanie ^{[16
]}

Barbiera, Giulia ^{[3
,4
]}

Soehnlein, Oliver ^{[11
]}

Gunzer, Matthias ^{[12
]}

Ginhoux, Florent ^{[5
]}

Sanchez-Cabo, Fatima ^{[2
]}

Nistal-Villan, Estanislao ^{[13
]}

Schulz, Christian ^{[14
,15
]}

Dopazo, Ana ^{[9
]}

Reinhardt, Christoph ^{[10
]}

Udalova, Irina A. ^{[8
]}

Ng, Lai Guan ^{[5
]}

Ostuni, Renato ^{[3
,4
]}

Hidalgo, Andres ^{[1
,11
]}

机构：

[1] Ctr Nacl Invest Cardiovasc Carlos III, Area Cell & Dev Biol, Madrid 28029, Spain

[2] Ctr Nacl Invest Cardiovasc Carlos III, Bioinformat Unit, Madrid 28029, Spain

[3] Univ Vita Salute San Raffaele, I-20132 Milan, Italy

[4] IRCCS San Raffaele Sci Inst, San Raffaele Telethon Inst Gene Therapy SR Tiget, I-20132 Milan, Italy

[5] ASTAR, Singapore Immunol Nework SIgN, Singapore 138648, Singapore

[6] Univ Castilla La Mancha, Dept Math, Ciudad Real 13001, Spain

[7] Univ Castilla La Mancha, MOLAB Math Oncol Lab, Ciudad Real 13001, Spain

[8] Univ Oxford, Kennedy Inst Rheumatol, Oxford OX3 7FY, England

[9] Ctr Nacl Invest Cardiovasc Carlos III, Genom Unit, Madrid 28029, Spain

[10] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Ctr Thrombosis & Hemostasis Mainz CTH, D-55131 Mainz, Germany

[11] Ludwig Maximillians Univ, Inst Cardiovasc Prevent IPEK, D-80802 Munich, Germany

[12] Univ Duisburg Essen, Univ Hosp, Inst Expt Immunol & Imaging, D-445141 Essen, Germany

[13] Univ CEU San Pablo, Fac Farm, Dept Pharmacol & Hlth Sci, Microbiol Sect, Madrid 28668, Spain

[14] Ludwig Maximilians Univ Munchen, LMU Klinikum, Med Klin & Poliklin 1, D-80336 Munich, Germany

[15] DZHK German Ctr Cardiovasc Res, D-80802 Munich, Germany

[16] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Johann Joachim Becher Weg 30, D-55128 Mainz, Germany

来源：

CELL | 2020年 / 183卷 / 05期

基金：

欧洲研究理事会;

关键词：

MYELOID DIFFERENTIATION; HOMEOSTASIS; MODULATION; CXCR4; QUANTIFICATION; IDENTIFICATION; PROGENITOR; ORIGINATE; REVEALS; SUBSET;

D O I：

10.1016/j.cell.2020.10.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Classically considered short-lived and purely defensive leukocytes, neutrophils are unique in their fast and moldable response to stimulation. This plastic behavior may underlie variable and even antagonistic functions during inflammation or cancer. yet the full spectrum of neutrophil properties as they enter healthy tissues remains unexplored. Using a new model to track neutrophil fates, we found short but variable lifetimes across multiple tissues. Through analysis of the receptor, transcriptional, and chromatin accessibility landscapes, we identify varying neutrophil states and assign non-canonical functions, including vascular repair and hematopoietic homeostasis. Accordingly, depletion of neutrophils compromised angiogenesis during early age, genotoxic injury, and viral infection, and impaired hematopoietic recovery after irradiation. Neutrophils acquired these properties in target tissues, a process that, in the lungs, occurred in CXCL12-rich areas and relied on CXCR4. Our results reveal that tissues co-opt neutrophils en route for elimination to induce programs that support their physiological demands.

引用

页码：1282 / +

页数：34

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