Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia

被引：24

作者：

Pervizaj-Oruqaj, Learta ^{[1
,2
,3
,4
]}

Selvakumar, Balachandar ^{[1
,2
,5
,6
]}

Ferrero, Maximiliano Ruben ^{[1
,2
,3
,4
,5
,6
]}

Heiner, Monika ^{[1
,2
,3
,4
]}

Malainou, Christina ^{[1
,2
,3
,4
]}

Glaser, Rolf David ^{[3
,7
]}

Wilhelm, Jochen ^{[2
,3
,4
,8
]}

Bartkuhn, Marek ^{[3
,7
]}

Weiss, Astrid ^{[2
,4
,8
]}

Alexopoulos, Ioannis ^{[1
,2
,3
,4
]}

Witte, Biruta ^{[9
]}

Gattenlohner, Stefan ^{[10
]}

Vadasz, Istvan ^{[2
,3
,4
,8
]}

Morty, Rory Edward ^{[11
,12
]}

Seeger, Werner ^{[2
,3
,4
,5
,6
,8
]}

Schermuly, Ralph Theo ^{[2
,3
,4
,8
]}

Vazquez-Armendariz, Ana Ivonne ^{[1
,2
,3
,4
,13
]}

Herold, Susanne ^{[1
,2
,3
,4
]}

机构：

[1] Univ Giessen, Dept Internal Med, Giessen, Germany

[2] Justus Liebig Univ, Univ Hosp Giessen, Marburg Lung Ctr, Member German Ctr Lung Res DZL, Giessen, Germany

[3] Justus Liebig Univ, Inst Lung Hlth ILH, Giessen, Germany

[4] Excellence Cluster Cardio Pulm Inst CPI, Giessen, Germany

[5] Max Planck Inst Heart & Lung Res, Bad Nauheim, Germany

[6] Inst Invest Biomed Buenos Aires IBioBA, Buenos Aires, Argentina

[7] Justus Liebig Univ, Biomed Informat & Syst Med, Giessen, Germany

[8] Univ Giessen, Dept Internal Med 2, Giessen, Germany

[9] Univ Hosp Giessen, Dept Gen & Thorac Surg, Giessen, Germany

[10] Univ Hosp Giessen, Dept Pathol, Giessen, Germany

[11] Univ Hosp Heidelberg, Member German Ctr Lung Res DZL, Dept Translat Pulmonol, Heidelberg, Germany

[12] Univ Hosp Heidelberg, Translat Lung Res Ctr, Heidelberg, Germany

[13] Univ Bonn, Life & Med Sci Inst, Organoid Biol, Transdisciplinary Res Area Life & Hlth, Bonn, Germany

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

IDENTIFICATION; ACTIVATION; INFECTION; CELLS; POPULATION; MONOCYTES; MIGRATION; ADHESION; BARRIER; MARKER;

D O I：

10.1038/s41467-023-44421-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Influenza A virus (IAV) infectionmobilizes bone marrow-derived macrophages (BMDM) that gradually undergo transition to tissue-resident alveolar macrophages (TR-AM) in the inflamed lung. Combining high-dimensional single-cell transcriptomics with complex lung organoid modeling, in vivo adoptive cell transfer, and BMDM-specific gene targeting, we found that transitioning ("regenerative") BMDM and TR-AM highly express Placenta-expressed transcript 1 (Plet1). We reveal that Plet1 is released from alveolar macrophages, and acts as important mediator of macrophage-epithelial cross-talk during lung repair by inducing proliferation of alveolar epithelial cells and re-sealing of the epithelial barrier. Intratracheal administration of recombinant Plet1 early in the disease course attenuated viral lung injury and rescued mice from otherwise fatal disease, highlighting its therapeutic potential.

引用

页数：19

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