Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions

被引：490

作者：

Evrard, Maximilien ^{[1
,10
]}

Kwok, Immanuel W. H. ^{[1
,2
]}

Chong, Shu Zhen ^{[1
]}

Teng, Karen W. W. ^{[1
]}

Becht, Etienne ^{[1
]}

Chen, Jinmiao ^{[1
]}

Sieow, Je Lin ^{[1
]}

Penny, Hweixian Leong ^{[1
]}

Ching, Goh Chi ^{[1
]}

Devi, Sapna ^{[1
]}

Adrover, Jose Maria ^{[3
]}

Li, Jackson L. Y. ^{[1
,3
]}

Liong, Ka Hang ^{[1
]}

Tan, Leonard ^{[1
]}

Poon, Zhiyong ^{[4
]}

Foo, Shihui ^{[1
]}

Chua, Jia Wang ^{[1
]}

Su, I-Hsin ^{[2
]}

Balabanian, Karl ^{[5
]}

Bachelerie, Francois ^{[5
]}

Biswas, Subhra K. ^{[1
]}

Larbi, Anis ^{[1
]}

Hwang, William Y. K. ^{[4
]}

Madan, Vikas ^{[6
]}

Koeffler, H. Phillip ^{[6
,7
,8
]}

Wong, Siew Cheng ^{[1
]}

Newell, Evan W. ^{[1
]}

Hidalgo, Andres ^{[3
,9
]}

Ginhoux, Florent ^{[1
]}

Ng, Lai Guan ^{[1
,2
]}

机构：

[1] Agcy Sci Technol & Res, Singapore Immunol Network, Biopolis 138648, Singapore

[2] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore

[3] Fdn Ctr Nacl Invest Cardiovasc, Area Cell & Dev Biol, Madrid 28029, Spain

[4] Singapore Gen Hosp, Dept Hematol, Singapore 169856, Singapore

[5] Univ Paris Saclay, Univ Paris Sud, Inflammat Chemokines & Immunopathol, INSERM,Fac Med,UMR 996, F-92140 Clamart, France

[6] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117599, Singapore

[7] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Div Hematol Oncol, Los Angeles, CA 90048 USA

[8] Natl Univ Singapore Hosp, Natl Univ Canc Inst Singapore, Dept Hematol Oncol, Singapore 119074, Singapore

[9] LMU, Inst Cardiovasc Prevent, D-80336 Munich, Germany

[10] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic 3000, Australia

来源：

IMMUNITY | 2018年 / 48卷 / 02期

关键词：

HEMATOPOIETIC STEM-CELLS; TRANSCRIPTION FACTORS; MYELOID CELLS; IMMUNE-RESPONSES; C/EBP-EPSILON; HALF-LIVES; IN-VITRO; CANCER; INFLAMMATION; MACROPHAGES;

D O I：

10.1016/j.immuni.2018.02.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Neutrophils are specialized innate cells that require constant replenishment from proliferative bone marrow (BM) precursors as a result of their short half-life. Although it is established that neutrophils are derived from the granulocyte-macrophage progenitor (GMP), the differentiation pathways from GMP to functional mature neutrophils are poorly defined. Using mass cytometry (CyTOF) and cell-cycle-based analysis, we identified three neutrophil subsets within the BM: a committed proliferative neutrophil precursor (preNeu) which differentiates into non-proliferating immature neutrophils and mature neutrophils. Transcriptomic profiling and functional analysis revealed that preNeu require the C/EBP epsilon transcription factor for their generation from the GMP, and their proliferative program is substituted by a gain of migratory and effector function as they mature. preNeus expand under microbial and tumoral stress, and immature neutrophils are recruited to the periphery of tumor-bearing mice. In summary, our study identifies specialized BM granulocytic populations that ensure supply under homeostasis and stress responses.

引用

页码：364 / +

页数：24

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