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

Author

Listed:
  • Kuei-Pin Chung

    (National Taiwan University
    National Taiwan University Hospital)

  • Chih-Ning Cheng

    (National Taiwan University
    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
    National Taiwan University Hospital
    National Taiwan University)

  • Han-Chun Kuo

    (National Taiwan University)

  • Ya-Ting Lin

    (National Taiwan University
    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
    Fu Jen Catholic University)

  • Sheng-Yuan Ruan

    (National Taiwan University Hospital)

  • Jung-Yien Chien

    (National Taiwan University Hospital)

  • Maria Plataki

    (Weill Cornell Medicine
    New York Presbyterian Hospital-Weill Cornell Medical Center)

  • Suzanne M. Cloonan

    (Weill Cornell Medicine
    Trinity College Dublin)

  • Peter Carmeliet

    (KU Leuven, VIB Center for Cancer Biology
    Khalifa University of Science and Technology)

  • Augustine M. K. Choi

    (Weill Cornell Medicine
    New York Presbyterian Hospital-Weill Cornell Medical Center)

  • Ching-Hua Kuo

    (National Taiwan University
    National Taiwan University
    National Taiwan University Hospital)

  • Chong-Jen Yu

    (National Taiwan University Hospital
    National Taiwan University Hospital Hsin-Chu Branch
    National Taiwan University)

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.

Suggested Citation

  • 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 R, 2024. "Alveolar epithelial cells mitigate neutrophilic inflammation in lung injury through regulating mitochondrial fatty acid oxidation," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51683-1
    DOI: 10.1038/s41467-024-51683-1
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