2. Academic Validation
  3. Alveolar epithelial cells mitigate neutrophilic inflammation in lung injury through regulating mitochondrial fatty acid oxidation

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

  • Nat Commun. 2024 Aug 22;15(1):7241. doi: 10.1038/s41467-024-51683-1.
Kuei-Pin Chung 1 2,  Chih-Ning Cheng 3 4,  Yi-Jung Chen 5,  Chia-Lang Hsu 6,  Yen-Lin Huang 7,  Min-Shu Hsieh 7 8 9,  Han-Chun Kuo 4,  Ya-Ting Lin 3 4,  Yi-Hsiu Juan 10,  Kiichi Nakahira 11,  Yen-Fu Chen 12,  Wei-Lun Liu 13 14,  Sheng-Yuan Ruan 10,  Jung-Yien Chien 10,  Maria Plataki 15 16,  Suzanne M Cloonan 15 17,  Peter Carmeliet 18 19,  Augustine M K Choi 15 16,  Ching-Hua Kuo 20 21 22,  Chong-Jen Yu 23 24 25
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. gbchung@ntu.edu.tw.
  • 2 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan. gbchung@ntu.edu.tw.
  • 3 School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 4 The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
  • 5 Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 6 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
  • 7 Department of Pathology, National Taiwan University Cancer Center, Taipei, Taiwan.
  • 8 Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
  • 9 Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 10 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • 11 Department of Pharmacology, Nara Medical University, Kashihara, Nara, Japan.
  • 12 Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.
  • 13 School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan.
  • 14 Department of Critical Care Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei, Taiwan.
  • 15 Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  • 16 New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY, USA.
  • 17 School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
  • 18 Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven, Belgium.
  • 19 Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
  • 20 School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. kuoch@ntu.edu.tw.
  • 21 The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan. kuoch@ntu.edu.tw.
  • 22 Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan. kuoch@ntu.edu.tw.
  • 23 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. jefferycjyu@ntu.edu.tw.
  • 24 Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan. jefferycjyu@ntu.edu.tw.
  • 25 Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. jefferycjyu@ntu.edu.tw.
PMID: 39174557 DOI: 10.1038/s41467-024-51683-1
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.

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