Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution

被引：13

作者：

Hsu, Alan Y. ^{[1
,2
,3
]}

Huang, Qingxiang ^{[4
]}

Pi, Xiong ^{[5
]}

Fu, Jianing ^{[5
]}

Raghunathan, Krishnan ^{[6
]}

Ghimire, Laxman ^{[1
,2
,3
]}

Balasubramanian, Arumugam ^{[1
,2
,3
]}

Xie, Xuemei ^{[1
,2
,3
]}

Yu, Hongbo ^{[7
]}

Loison, Fabien ^{[1
,2
,3
]}

Haridas, Viraga ^{[8
]}

Zha, Jiali ^{[1
,2
,3
]}

Liu, Fei ^{[1
,2
,3
]}

Park, Shin-young ^{[1
,2
,3
]}

Bagale, Kamal ^{[9
]}

Ren, Qian ^{[4
]}

Fan, Yuping ^{[4
]}

Zheng, Yi ^{[10
]}

Cancelas, Jose A. ^{[10
,11
]}

Chai, Li ^{[1
,2
,3
]}

Stowell, Sean R. ^{[1
,2
,3
]}

Chen, Kanchao ^{[4
]}

Xu, Rong ^{[1
,2
,3
]}

Wang, Xiaoxue ^{[12
]}

Xu, Yuanfu ^{[4
]}

Zhang, Lianghui ^{[9
]}

Cheng, Tao ^{[4
]}

Ma, Fengxia ^{[4
]}

Thiagarajah, Jay R. ^{[13
]}

Wu, Hao ^{[5
]}

Feng, Sizhou ^{[4
]}

Luo, Hongbo R. ^{[1
,2
,3
]}

机构：

[1] Harvard Med Sch, Dept Pathol, PhD Program Immunol, Boston, MA 02115 USA

[2] Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA

[3] Mass Gen Brigham, Dept Pathol, Boston, MA 02115 USA

[4] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Expt Hematol, Natl Clin Res Ctr Blood Dis, Inst Hematol & Blood Dis Hosp, Tianjin 300020, Peoples R China

[5] Harvard Med Sch, Boston Childrens Hosp, Dept Biol Chem & Mol Pharmacol, Program Cellular & Mol Med, Boston, MA 20115 USA

[6] Harvard Med Sch, Boston Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Boston, MA 20115 USA

[7] VA Boston Healthcare Syst, Dept Pathol & Lab Med, Boston, MA 02132 USA

[8] Boston Childrens Hosp, Flow & Imaging Cytometry Resources, Boston, MA 02115 USA

[9] Univ Pittsburgh, Ctr Vaccine Res, Sch Med, Div Pulm Allergy Crit Care & Sleep Med, Pittsburgh, PA 15261 USA

[10] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Hoxworth Blood Ctr, Expt Hematol & Canc Biol Res,Coll Med, Cincinnati, OH 45229 USA

[11] Dana Farber Canc Inst, Connell & OReilly Families Cell Manipulat Core Fac, Boston, MA 02115 USA

[12] Univ Chinese Acad Sci, Beijing 101408, Peoples R China

[13] Boston Childrens Hosp, Harvard Digest Dis Ctr, Congenital Enteropathy Program, PediCODE Consortium, Boston, MA USA

来源：

CELL | 2025年 / 188卷 / 06期

基金：

美国国家卫生研究院;

关键词：

DECAY-ACCELERATING FACTOR; EXPRESSION; APOPTOSIS; EXOSOMES; CD55; MICROVESICLES; DESTRUCTION; MIGRASOME; MEMBRANE; RELEASE;

D O I：

10.1016/j.cell.2025.01.021

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：

Although subsets with immunosuppressive properties exist, neutrophils are typically known for their pro-inflammatory role and pathogen clearance capabilities. Here, we reveal that neutrophils can paradoxically aid in resolving inflammation by actively producing anti-inflammatory extracellular vesicles. These large agingneutrophil-derived vesicles (LAND-Vs) do not fit into classical vesicle categorizations due to their specific size, structure, or biogenesis pathway. They are protected from efferocytotic clearance by phagocytes due to surface "do not eat me"signals and accumulate in the resolution phase of inflammation. CD55 on LAND-Vs exerts a robust, sustained anti-inflammatory effect by inhibiting complement 3 convertase, thereby reducing neutrophil recruitment and tissue damage. CD55+ LAND-Vs originate in ordered lipid raft domains, where CD55 accumulates asymmetrically during neutrophil aging, and are subsequently formed through RhoA-dependent budding. Collectively, LAND-V emerges as a pivotal physiological immunomodulator and showcases functions that transcend the limited lifespan of neutrophils, offering a therapeutic target for inflammatory and infectious diseases.

引用

页码：1623 / 1641.e26

页数：46

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