IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51683-1.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51683-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-51683-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Johannes C. Melms & Jana Biermann & Huachao Huang & Yiping Wang & Ajay Nair & Somnath Tagore & Igor Katsyv & André F. Rendeiro & Amit Dipak Amin & Denis Schapiro & Chris J. Frangieh & Adrienne M. Luom, 2021. "Author Correction: A molecular single-cell lung atlas of lethal COVID-19," Nature, Nature, vol. 598(7882), pages 2-2, October.
    2. Dannielle DeWaal & Veronique Nogueira & Alexander R. Terry & Krushna C. Patra & Sang-Min Jeon & Grace Guzman & Jennifer Au & Christopher P. Long & Maciek R. Antoniewicz & Nissim Hay, 2018. "Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    3. Hiroaki Sunaga & Hiroki Matsui & Manabu Ueno & Toshitaka Maeno & Tatsuya Iso & Mas Rizky A. A. Syamsunarno & Saki Anjo & Takashi Matsuzaka & Hitoshi Shimano & Tomoyuki Yokoyama & Masahiko Kurabayashi, 2013. "Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice," Nature Communications, Nature, vol. 4(1), pages 1-14, December.
    4. Hiroaki Sunaga & Hiroki Matsui & Manabu Ueno & Toshitaka Maeno & Tatsuya Iso & Mas Rizky A.A. Syamsunarno & Saki Anjo & Takashi Matsuzaka & Hitoshi Shimano & Tomoyuki Yokoyama & Masahiko Kurabayashi, 2013. "Erratum: Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice," Nature Communications, Nature, vol. 4(1), pages 1-2, December.
    5. Barbara Treutlein & Doug G. Brownfield & Angela R. Wu & Norma F. Neff & Gary L. Mantalas & F. Hernan Espinoza & Tushar J. Desai & Mark A. Krasnow & Stephen R. Quake, 2014. "Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq," Nature, Nature, vol. 509(7500), pages 371-375, May.
    6. Dannielle DeWaal & Veronique Nogueira & Alexander R. Terry & Krushna C. Patra & Sang-Min Jeon & Grace Guzman & Jennifer Au & Christopher P. Long & Maciek R. Antoniewicz & Nissim Hay, 2018. "Author Correction: Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
    7. Tushar J. Desai & Douglas G. Brownfield & Mark A. Krasnow, 2014. "Alveolar progenitor and stem cells in lung development, renewal and cancer," Nature, Nature, vol. 507(7491), pages 190-194, March.
    8. Johannes C. Melms & Jana Biermann & Huachao Huang & Yiping Wang & Ajay Nair & Somnath Tagore & Igor Katsyv & André F. Rendeiro & Amit Dipak Amin & Denis Schapiro & Chris J. Frangieh & Adrienne M. Luom, 2021. "A molecular single-cell lung atlas of lethal COVID-19," Nature, Nature, vol. 595(7865), pages 114-119, July.
    9. Toni M. Delorey & Carly G. K. Ziegler & Graham Heimberg & Rachelly Normand & Yiming Yang & Åsa Segerstolpe & Domenic Abbondanza & Stephen J. Fleming & Ayshwarya Subramanian & Daniel T. Montoro & Karth, 2021. "COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets," Nature, Nature, vol. 595(7865), pages 107-113, July.
    10. Sandra Schoors & Ulrike Bruning & Rindert Missiaen & Karla C. S. Queiroz & Gitte Borgers & Ilaria Elia & Annalisa Zecchin & Anna Rita Cantelmo & Stefan Christen & Jermaine Goveia & Ward Heggermont & L, 2015. "Correction: Corrigendum: Fatty acid carbon is essential for dNTP synthesis in endothelial cells," Nature, Nature, vol. 526(7571), pages 144-144, October.
    11. Kuei-Pin Chung & Chia-Lang Hsu & Li-Chao Fan & Ziling Huang & Divya Bhatia & Yi-Jung Chen & Shu Hisata & Soo Jung Cho & Kiichi Nakahira & Mitsuru Imamura & Mary E. Choi & Chong-Jen Yu & Suzanne M. Clo, 2019. "Mitofusins regulate lipid metabolism to mediate the development of lung fibrosis," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    12. Sandra Schoors & Ulrike Bruning & Rindert Missiaen & Karla C. S. Queiroz & Gitte Borgers & Ilaria Elia & Annalisa Zecchin & Anna Rita Cantelmo & Stefan Christen & Jermaine Goveia & Ward Heggermont & L, 2015. "Fatty acid carbon is essential for dNTP synthesis in endothelial cells," Nature, Nature, vol. 520(7546), pages 192-197, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xin Pan & Lan Wang & Juntang Yang & Yingge Li & Min Xu & Chenxi Liang & Lulu Liu & Zhongzheng Li & Cong Xia & Jiaojiao Pang & Mengyuan Wang & Meng Li & Saiya Guo & Peishuo Yan & Chen Ding & Ivan O. Ro, 2024. "TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Benjamin Ng & Kevin Y. Huang & Chee Jian Pua & Sivakumar Viswanathan & Wei-Wen Lim & Fathima F. Kuthubudeen & Yu-Ning Liu & An An Hii & Benjamin L. George & Anissa A. Widjaja & Enrico Petretto & Stuar, 2024. "Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Maik Pietzner & Robert Lorenz Chua & Eleanor Wheeler & Katharina Jechow & Julian D. S. Willett & Helena Radbruch & Saskia Trump & Bettina Heidecker & Hugo Zeberg & Frank L. Heppner & Roland Eils & Mar, 2022. "ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Xiaolei Wang & Terrence Tsz-Tai Yuen & Ying Dou & Jingchu Hu & Renhao Li & Zheng Zeng & Xuansheng Lin & Huarui Gong & Celia Hoi-Ching Chan & Chaemin Yoon & Huiping Shuai & Deborah Tip-Yin Ho & Ivan Fa, 2023. "Vaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Laura Heydemann & Małgorzata Ciurkiewicz & Georg Beythien & Kathrin Becker & Klaus Schughart & Stephanie Stanelle-Bertram & Berfin Schaumburg & Nancy Mounogou-Kouassi & Sebastian Beck & Martin Zickler, 2023. "Hamster model for post-COVID-19 alveolar regeneration offers an opportunity to understand post-acute sequelae of SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Minzhe Guo & Michael P. Morley & Cheng Jiang & Yixin Wu & Guangyuan Li & Yina Du & Shuyang Zhao & Andrew Wagner & Adnan Cihan Cakar & Michal Kouril & Kang Jin & Nathan Gaddis & Joseph A. Kitzmiller & , 2023. "Guided construction of single cell reference for human and mouse lung," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. Praveen Weeratunga & Laura Denney & Joshua A. Bull & Emmanouela Repapi & Martin Sergeant & Rachel Etherington & Chaitanya Vuppussetty & Gareth D. H. Turner & Colin Clelland & Jeongmin Woo & Amy Cross , 2023. "Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    8. Christopher W. Murray & Jennifer J. Brady & Mingqi Han & Hongchen Cai & Min K. Tsai & Sarah E. Pierce & Ran Cheng & Janos Demeter & David M. Feldser & Peter K. Jackson & David B. Shackelford & Monte M, 2022. "LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    9. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Christina Beck & Deepak Ramanujam & Paula Vaccarello & Florenc Widenmeyer & Martin Feuerherd & Cho-Chin Cheng & Anton Bomhard & Tatiana Abikeeva & Julia Schädler & Jan-Peter Sperhake & Matthias Graw &, 2023. "Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    11. Pablo Jané & Xiaoying Xu & Vincent Taelman & Eduardo Jané & Karim Gariani & Rebecca A. Dumont & Yonathan Garama & Francisco Kim & María Val Gomez & Martin A. Walter, 2023. "The Imageable Genome," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Balkrishna Chaube & Kathryn M. Citrin & Mahnaz Sahraei & Abhishek K. Singh & Diego Saenz Urturi & Wen Ding & Richard W. Pierce & Raaisa Raaisa & Rebecca Cardone & Richard Kibbey & Carlos Fernández-Her, 2023. "Suppression of angiopoietin-like 4 reprograms endothelial cell metabolism and inhibits angiogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    13. Dhiraj K. Singh & Ekaterina Aladyeva & Shibali Das & Bindu Singh & Ekaterina Esaulova & Amanda Swain & Mushtaq Ahmed & Journey Cole & Chivonne Moodley & Smriti Mehra & Larry S. Schlesinger & Maxim N. , 2022. "Myeloid cell interferon responses correlate with clearance of SARS-CoV-2," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Vincent Geldhof & Laura P. M. H. Rooij & Liliana Sokol & Jacob Amersfoort & Maxim Schepper & Katerina Rohlenova & Griet Hoste & Adriaan Vanderstichele & Anne-Marie Delsupehe & Edoardo Isnaldi & Naima , 2022. "Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    15. Aleksandr Ianevski & Anil K. Giri & Tero Aittokallio, 2022. "Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    16. Zhoufeng Wang & Zhe Li & Kun Zhou & Chengdi Wang & Lili Jiang & Li Zhang & Ying Yang & Wenxin Luo & Wenliang Qiao & Gang Wang & Yinyun Ni & Shuiping Dai & Tingting Guo & Guiyi Ji & Minjie Xu & Yiying , 2021. "Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    17. Guangyuan Li & Baobao Song & Harinder Singh & V. B. Surya Prasath & H. Leighton Grimes & Nathan Salomonis, 2023. "Decision level integration of unimodal and multimodal single cell data with scTriangulate," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Jingyang Qian & Jie Liao & Ziqi Liu & Ying Chi & Yin Fang & Yanrong Zheng & Xin Shao & Bingqi Liu & Yongjin Cui & Wenbo Guo & Yining Hu & Hudong Bao & Penghui Yang & Qian Chen & Mingxiao Li & Bing Zha, 2023. "Reconstruction of the cell pseudo-space from single-cell RNA sequencing data with scSpace," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    19. Catherine S. Blaha & Gopalakrishnan Ramakrishnan & Sang-Min Jeon & Veronique Nogueira & Hyunsoo Rho & Soeun Kang & Prashanth Bhaskar & Alexander R. Terry & Alexandre F. Aissa & Maxim V. Frolov & Krush, 2022. "A non-catalytic scaffolding activity of hexokinase 2 contributes to EMT and metastasis," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    20. Yi Lei & Qiangyun Liu & Binggui Chen & Fangfang Wu & Yiming Li & Xue Dong & Nina Ma & Ziru Wu & Yanfang Zhu & Lu Wang & Yuxin Fu & Yuming Liu & Yinting Song & Mei Du & Heng Zhang & Jidong Zhu & Timoth, 2024. "Protein O-GlcNAcylation coupled to Hippo signaling drives vascular dysfunction in diabetic retinopathy," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51683-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.