Alveolar epithelial cells mitigate neutrophilic inflammation in lung injury through regulating mitochondrial fatty acid oxidation

Kuei-Pin Chung (), Chih-Ning Cheng, Yi-Jung Chen, Chia-Lang Hsu, Yen-Lin Huang, Min-Shu Hsieh, Han-Chun Kuo, Ya-Ting Lin, Yi-Hsiu Juan, Kiichi Nakahira, Yen-Fu Chen, Wei-Lun Liu, Sheng-Yuan Ruan, Jung-Yien Chien, Maria Plataki, Suzanne M. Cloonan, Peter Carmeliet, Augustine M. K. Choi, Ching-Hua Kuo () and Chong-Jen Yu ()
Additional contact information
Kuei-Pin Chung: National Taiwan University
Chih-Ning Cheng: National Taiwan University
Yi-Jung Chen: National Taiwan University
Chia-Lang Hsu: National Taiwan University Hospital
Yen-Lin Huang: National Taiwan University Cancer Center
Min-Shu Hsieh: National Taiwan University Cancer Center
Han-Chun Kuo: National Taiwan University
Ya-Ting Lin: National Taiwan University
Yi-Hsiu Juan: National Taiwan University Hospital
Kiichi Nakahira: Nara Medical University
Yen-Fu Chen: National Taiwan University Hospital Yunlin Branch
Wei-Lun Liu: Fu Jen Catholic University
Sheng-Yuan Ruan: National Taiwan University Hospital
Jung-Yien Chien: National Taiwan University Hospital
Maria Plataki: Weill Cornell Medicine
Suzanne M. Cloonan: Weill Cornell Medicine
Peter Carmeliet: KU Leuven, VIB Center for Cancer Biology
Augustine M. K. Choi: Weill Cornell Medicine
Ching-Hua Kuo: National Taiwan University
Chong-Jen Yu: National Taiwan University Hospital

Nature Communications, 2024, vol. 15, issue 1, 1-23

Abstract: Abstract Type 2 alveolar epithelial (AT2) cells of the lung are fundamental in regulating alveolar inflammation in response to injury. Impaired mitochondrial long-chain fatty acid β-oxidation (mtLCFAO) in AT2 cells is assumed to aggravate alveolar inflammation in acute lung injury (ALI), yet the importance of mtLCFAO to AT2 cell function needs to be defined. Here we show that expression of carnitine palmitoyltransferase 1a (CPT1a), a mtLCFAO rate limiting enzyme, in AT2 cells is significantly decreased in acute respiratory distress syndrome (ARDS). In mice, Cpt1a deletion in AT2 cells impairs mtLCFAO without reducing ATP production and alters surfactant phospholipid abundance in the alveoli. Impairing mtLCFAO in AT2 cells via deleting either Cpt1a or Acadl (acyl-CoA dehydrogenase long chain) restricts alveolar inflammation in ALI by hindering the production of the neutrophilic chemokine CXCL2 from AT2 cells. This study thus highlights mtLCFAO as immunometabolism to injury in AT2 cells and suggests impaired mtLCFAO in AT2 cells as an anti-inflammatory response in ARDS.

Date: 2024
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DOI: 10.1038/s41467-024-51683-1

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