Early-age efferocytosis directs macrophage arachidonic acid metabolism for tissue regeneration

被引：0

作者：

Lantz, Connor ^{[1
]}

Becker, Amanda ^{[2
]}

Deberge, Matthew ^{[1
]}

Filipp, Mallory ^{[1
]}

Glinton, Kristofor ^{[1
]}

Ananthakrishnan, Aparnaa ^{[1
]}

Urbanczyk, Jessica ^{[1
]}

Cetlin, Madeline ^{[1
]}

Alzamroon, Afnan ^{[3
]}

Abdel-Latif, Ahmed ^{[3
]}

Spite, Matthew ^{[4
]}

Ge, Zhi-Dong ^{[1
]}

Thorp, Edward B. ^{[1
,2
,5
]}

机构：

[1] Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA

[2] Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA

[3] Harvard Med Sch, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Boston, MA USA

[4] Ann & Robert Lurie Childrens Hosp, Stanley Manne Childrens Res Inst, Heart Ctr, Chicago, IL 60611 USA

[5] Northwestern Univ, Comprehens Transplant Ctr, Feinberg Sch Med, Chicago, IL 60611 USA

来源：

IMMUNITY | 2025年 / 58卷 / 02期

基金：

美国国家卫生研究院;

关键词：

THROMBOXANE A(2); APOPTOTIC CELLS; CARDIAC MACROPHAGES; TAM RECEPTORS; GENE; INFLAMMATION; EXPRESSION; PHAGOCYTOSIS; CLEARANCE; PATHWAY;

D O I：

10.1016/j.immuni.2024.11.018

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

In response to organ injury in adults, macrophages often promote scarring, yet during early life, they are required for tissue regeneration. To elucidate the mechanisms underlying age-associated regeneration, we compared the macrophage injury response in newborn versus adult hearts. Single-cell analysis revealed an accumulation of tissue-resident macrophages in neonates that were selectively polarized for apoptotic cell recognition and uptake (efferocytosis). Ablation of the apoptotic cell recognition receptor Mertk in newborns prevented cardiac regeneration. These findings could be attributed to reprogramming of macrophage gene expression that was required for biosynthesis of the eicosanoid thromboxane A2, which unexpectedly activated parenchymal cell proliferation. Markers of thromboxane A2 production were suppressed in adult macrophages after efferocytosis. Moreover, macrophage-neighboring neonatal cardiomyocytes expressed the thromboxane A2 receptor, whose activation induced a metabolic shift that supported cellular proliferation. Our data reveal a fundamental age-defined macrophage response in which lipid mitogens produced during efferocytosis support receptor-mediated tissue regeneration.

引用

页码：344 / 361.e7

页数：26

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