IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v586y2020i7829d10.1038_s41586-020-2799-2.html
   My bibliography  Save this article

A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis

Author

Listed:
  • Mingming Zhang

    (Cornell University
    Cornell University)

  • Lixing Zhou

    (Sichuan University)

  • Yuejie Xu

    (Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University and Nanjing Medical University)

  • Min Yang

    (Cornell University)

  • Yilai Xu

    (Cornell University)

  • Garrison Paul Komaniecki

    (Cornell University)

  • Tatsiana Kosciuk

    (Cornell University)

  • Xiao Chen

    (Cornell University)

  • Xuan Lu

    (Cornell University)

  • Xiaoping Zou

    (Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University and Nanjing Medical University)

  • Maurine E. Linder

    (Cornell University)

  • Hening Lin

    (Cornell University
    Cornell University)

Abstract

Cysteine palmitoylation (S-palmitoylation) is a reversible post-translational modification that is installed by the DHHC family of palmitoyltransferases and is reversed by several acyl protein thioesterases1,2. Although thousands of human proteins are known to undergo S-palmitoylation, how this modification is regulated to modulate specific biological functions is poorly understood. Here we report that the key T helper 17 (TH17) cell differentiation stimulator, STAT33,4, is subject to reversible S-palmitoylation on cysteine 108. DHHC7 palmitoylates STAT3 and promotes its membrane recruitment and phosphorylation. Acyl protein thioesterase 2 (APT2, also known as LYPLA2) depalmitoylates phosphorylated STAT3 (p-STAT3) and enables it to translocate to the nucleus. This palmitoylation–depalmitoylation cycle enhances STAT3 activation and promotes TH17 cell differentiation; perturbation of either palmitoylation or depalmitoylation negatively affects TH17 cell differentiation. Overactivation of TH17 cells is associated with several inflammatory diseases, including inflammatory bowel disease (IBD). In a mouse model, pharmacological inhibition of APT2 or knockout of Zdhhc7—which encodes DHHC7—relieves the symptoms of IBD. Our study reveals not only a potential therapeutic strategy for the treatment of IBD but also a model through which S-palmitoylation regulates cell signalling, which might be broadly applicable for understanding the signalling functions of numerous S-palmitoylation events.

Suggested Citation

  • Mingming Zhang & Lixing Zhou & Yuejie Xu & Min Yang & Yilai Xu & Garrison Paul Komaniecki & Tatsiana Kosciuk & Xiao Chen & Xuan Lu & Xiaoping Zou & Maurine E. Linder & Hening Lin, 2020. "A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis," Nature, Nature, vol. 586(7829), pages 434-439, October.
  • Handle: RePEc:nat:nature:v:586:y:2020:i:7829:d:10.1038_s41586-020-2799-2
    DOI: 10.1038/s41586-020-2799-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-020-2799-2
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-020-2799-2?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Shiman Zuo & Yuxin Wang & Hanjing Bao & Zehui Zhang & Nanfei Yang & Meng Jia & Qing Zhang & Ani Jian & Rong Ji & Lidan Zhang & Yan Lu & Yahong Huang & Pingping Shen, 2024. "Lipid synthesis, triggered by PPARγ T166 dephosphorylation, sustains reparative function of macrophages during tissue repair," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Lu Jia & Yiyang Jiang & Lili Wu & Jingfei Fu & Juan Du & Zhenhua Luo & Lijia Guo & Junji Xu & Yi Liu, 2024. "Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Wen-Lan Yang & Weinan Qiu & Ting Zhang & Kai Xu & Zi-Juan Gu & Yu Zhou & Heng-Ji Xu & Zhong-Zhou Yang & Bin Shen & Yong-Liang Zhao & Qi Zhou & Ying Yang & Wei Li & Peng-Yuan Yang & Yun-Gui Yang, 2023. "Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Hai Ni & Yinuo Wang & Kai Yao & Ling Wang & Jiancheng Huang & Yongfang Xiao & Hongyao Chen & Bo Liu & Cliff Y. Yang & Jijun Zhao, 2024. "Cyclical palmitoylation regulates TLR9 signalling and systemic autoimmunity in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, 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:nature:v:586:y:2020:i:7829:d:10.1038_s41586-020-2799-2. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.