IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-44179-x.html
   My bibliography  Save this article

Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling

Author

Listed:
  • Jingyun Quan

    (Guangdong Medical University
    Affiliated Hospital of Guangdong Medical University)

  • Xiaoxia Wen

    (Affiliated Hospital of Guangdong Medical University)

  • Guomei Su

    (Affiliated Hospital of Guangdong Medical University)

  • Yu Zhong

    (Affiliated Hospital of Guangdong Medical University)

  • Tong Huang

    (Affiliated Hospital of Guangdong Medical University)

  • Zhilin Xiong

    (Affiliated Hospital of Guangdong Medical University)

  • Jiewen Huang

    (Affiliated Hospital of Guangdong Medical University)

  • Yingying Lv

    (Guangdong Medical University)

  • Shihai Li

    (Affiliated Hospital of Guangdong Medical University)

  • Shuhua Luo

    (Affiliated Hospital of Guangdong Medical University)

  • Chaole Luo

    (Guangdong Medical University)

  • Xin Cai

    (Affiliated Hospital of Guangdong Medical University)

  • Xianwen Lai

    (Affiliated Hospital of Guangdong Medical University)

  • Yuanyuan Xiang

    (Affiliated Hospital of Guangdong Medical University)

  • Song Guo Zheng

    (Guangdong Medical University)

  • Yiming Shao

    (Guangdong Medical University)

  • Haitao Lin

    (Affiliated Hospital of Guangdong Medical University)

  • Xiao Gao

    (Affiliated Hospital of Guangdong Medical University)

  • Jing Tang

    (Affiliated Hospital of Guangdong Medical University)

  • Tianwen Lai

    (Guangdong Medical University
    Affiliated Hospital of Guangdong Medical University)

Abstract

Dysregulation of IL-17A is closely associated with airway inflammation and remodeling in severe asthma. However, the molecular mechanisms by which IL-17A is regulated remain unclear. Here we identify epithelial sirtuin 6 (SIRT6) as an epigenetic regulator that governs IL-17A pathogenicity in severe asthma. Mice with airway epithelial cell-specific deletion of Sirt6 are protected against allergen-induced airway inflammation and remodeling via inhibiting IL-17A-mediated inflammatory chemokines and mesenchymal reprogramming. Mechanistically, SIRT6 directly interacts with RORγt and mediates RORγt deacetylation at lysine 192 via its PPXY motifs. SIRT6 promotes RORγt recruitment to the IL-17A gene promoter and enhances its transcription. In severe asthma patients, high expression of SIRT6 positively correlates with airway remodeling and disease severity. SIRT6 inhibitor (OSS_128167) treatment significantly attenuates airway inflammation and remodeling in mice. Collectively, these results uncover a function for SIRT6 in regulating IL-17A pathogenicity in severe asthma, implicating SIRT6 as a potential therapeutic target for severe asthma.

Suggested Citation

  • Jingyun Quan & Xiaoxia Wen & Guomei Su & Yu Zhong & Tong Huang & Zhilin Xiong & Jiewen Huang & Yingying Lv & Shihai Li & Shuhua Luo & Chaole Luo & Xin Cai & Xianwen Lai & Yuanyuan Xiang & Song Guo Zhe, 2023. "Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44179-x
    DOI: 10.1038/s41467-023-44179-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44179-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44179-x?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. Xiaofeng Zheng & Julienne L. Carstens & Jiha Kim & Matthew Scheible & Judith Kaye & Hikaru Sugimoto & Chia-Chin Wu & Valerie S. LeBleu & Raghu Kalluri, 2015. "Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer," Nature, Nature, vol. 527(7579), pages 525-530, November.
    2. Alan K. Okada & Kazuki Teranishi & Mark R. Ambroso & Jose Mario Isas & Elena Vazquez-Sarandeses & Joo-Yeun Lee & Arthur Alves Melo & Priyatama Pandey & Daniel Merken & Leona Berndt & Michael Lammers &, 2021. "Lysine acetylation regulates the interaction between proteins and membranes," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    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. Ankur Chakravarthy & Ian Reddin & Stephen Henderson & Cindy Dong & Nerissa Kirkwood & Maxmilan Jeyakumar & Daniela Rothschild Rodriguez & Natalia Gonzalez Martinez & Jacqueline McDermott & Xiaoping Su, 2022. "Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Sandhya Malla & Kanchan Kumari & Carlos A. García-Prieto & Jonatan Caroli & Anna Nordin & Trinh T. T. Phan & Devi Prasad Bhattarai & Carlos Martinez-Gamero & Eshagh Dorafshan & Stephanie Stransky & Da, 2024. "The scaffolding function of LSD1 controls DNA methylation in mouse ESCs," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    3. Mariel C. Paul & Christian Schneeweis & Chiara Falcomatà & Chuan Shan & Daniel Rossmeisl & Stella Koutsouli & Christine Klement & Magdalena Zukowska & Sebastian A. Widholz & Moritz Jesinghaus & Konsta, 2023. "Non-canonical functions of SNAIL drive context-specific cancer progression," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    4. Paul T. Morse & Gonzalo Pérez-Mejías & Junmei Wan & Alice A. Turner & Inmaculada Márquez & Hasini A. Kalpage & Asmita Vaishnav & Matthew P. Zurek & Philipp P. Huettemann & Katherine Kim & Tasnim Arrou, 2023. "Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Lining Liang & Hao Sun & Wei Zhang & Mengdan Zhang & Xiao Yang & Rui Kuang & Hui Zheng, 2016. "Meta-Analysis of EMT Datasets Reveals Different Types of EMT," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-22, June.
    6. Chuan Qin & Leonie G. Graf & Kilian Striska & Markus Janetzky & Norman Geist & Robin Specht & Sabrina Schulze & Gottfried J. Palm & Britta Girbardt & Babett Dörre & Leona Berndt & Stefan Kemnitz & Mar, 2024. "Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    7. Simon Maria Kienle & Tobias Schneider & Katrin Stuber & Christoph Globisch & Jasmin Jansen & Florian Stengel & Christine Peter & Andreas Marx & Michael Kovermann & Martin Scheffner, 2022. "Electrostatic and steric effects underlie acetylation-induced changes in ubiquitin structure and function," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:14:y:2023:i:1:d:10.1038_s41467-023-44179-x. 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.