IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32846-4.html
   My bibliography  Save this article

Sirtuin 6 maintains epithelial STAT6 activity to support intestinal tuft cell development and type 2 immunity

Author

Listed:
  • Xiwen Xiong

    (Xinxiang Medical University
    Xinxiang Medical University)

  • Chenyan Yang

    (Xinxiang Medical University
    Xinxiang Medical University)

  • Wei-Qi He

    (Suzhou Medical College of Soochow University)

  • Jiahui Yu

    (Xinxiang Medical University
    Xinxiang Medical University)

  • Yue Xin

    (Xinxiang Medical University
    Xinxiang Medical University)

  • Xinge Zhang

    (Xinxiang Medical University
    Xinxiang Medical University)

  • Rong Huang

    (Xinxiang Medical University
    Xinxiang Medical University)

  • Honghui Ma

    (Xinxiang Medical University
    Xinxiang Medical University)

  • Shaofang Xu

    (Suzhou Medical College of Soochow University)

  • Zun Li

    (Xinxiang Medical University
    Xinxiang Medical University)

  • Jie Ma

    (Xinxiang Medical University)

  • Lin Xu

    (Xinxiang Medical University)

  • Qunyi Wang

    (The Third Affiliated Hospital of Xinxiang Medical University)

  • Kaiqun Ren

    (Hunan Normal University School of Medicine)

  • Xiaoli S. Wu

    (Cold Spring Harbor Laboratory)

  • Christopher R. Vakoc

    (Cold Spring Harbor Laboratory)

  • Jiateng Zhong

    (Xinxiang Medical University)

  • Genshen Zhong

    (Xinxiang Medical University)

  • Xiaofei Zhu

    (Xinxiang Medical University)

  • Yu Song

    (Xinxiang Medical University)

  • Hai-Bin Ruan

    (University of Minnesota Medical School)

  • Qingzhi Wang

    (Xinxiang Medical University)

Abstract

Dynamic regulation of intestinal epithelial cell (IEC) differentiation is crucial for both homeostasis and the response to helminth infection. SIRT6 belongs to the NAD+-dependent deacetylases and has established diverse roles in aging, metabolism and disease. Here, we report that IEC Sirt6 deletion leads to impaired tuft cell development and type 2 immunity in response to helminth infection, thereby resulting in compromised worm expulsion. Conversely, after helminth infection, IEC SIRT6 transgenic mice exhibit enhanced epithelial remodeling process and more efficient worm clearance. Mechanistically, Sirt6 ablation causes elevated Socs3 expression, and subsequently attenuated tyrosine 641 phosphorylation of STAT6 in IECs. Notably, intestinal epithelial overexpression of constitutively activated STAT6 (STAT6vt) in mice is sufficient to induce the expansion of tuft and goblet cell linage. Furthermore, epithelial STAT6vt overexpression remarkedly reverses the defects in intestinal epithelial remodeling caused by Sirt6 ablation. Our results reveal a novel function of SIRT6 in regulating intestinal epithelial remodeling and mucosal type 2 immunity in response to helminth infection.

Suggested Citation

  • Xiwen Xiong & Chenyan Yang & Wei-Qi He & Jiahui Yu & Yue Xin & Xinge Zhang & Rong Huang & Honghui Ma & Shaofang Xu & Zun Li & Jie Ma & Lin Xu & Qunyi Wang & Kaiqun Ren & Xiaoli S. Wu & Christopher R. , 2022. "Sirtuin 6 maintains epithelial STAT6 activity to support intestinal tuft cell development and type 2 immunity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32846-4
    DOI: 10.1038/s41467-022-32846-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32846-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32846-4?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. Adam L. Haber & Moshe Biton & Noga Rogel & Rebecca H. Herbst & Karthik Shekhar & Christopher Smillie & Grace Burgin & Toni M. Delorey & Michael R. Howitt & Yarden Katz & Itay Tirosh & Semir Beyaz & Da, 2017. "A single-cell survey of the small intestinal epithelium," Nature, Nature, vol. 551(7680), pages 333-339, November.
    2. François Gerbe & Emmanuelle Sidot & Danielle J. Smyth & Makoto Ohmoto & Ichiro Matsumoto & Valérie Dardalhon & Pierre Cesses & Laure Garnier & Marie Pouzolles & Bénédicte Brulin & Marco Bruschi & Yvon, 2016. "Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites," Nature, Nature, vol. 529(7585), pages 226-230, January.
    3. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    4. Jakob von Moltke & Ming Ji & Hong-Erh Liang & Richard M. Locksley, 2016. "Tuft-cell-derived IL-25 regulates an intestinal ILC2–epithelial response circuit," Nature, Nature, vol. 529(7585), pages 221-225, January.
    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. Ihab Ansari & Llorenç Solé-Boldo & Meshi Ridnik & Julian Gutekunst & Oliver Gilliam & Maria Korshko & Timur Liwinski & Birgit Jickeli & Noa Weinberg-Corem & Michal Shoshkes-Carmel & Eli Pikarsky & Era, 2023. "TET2 and TET3 loss disrupts small intestine differentiation and homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Alberto Díez-Sánchez & Håvard T. Lindholm & Pia M. Vornewald & Jenny Ostrop & Rouan Yao & Andrew B. Single & Anne Marstad & Naveen Parmar & Tovah N. Shaw & Mara Martín-Alonso & Menno J. Oudhoff, 2024. "LSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Ryan N. O’Keefe & Annalisa L. E. Carli & David Baloyan & David Chisanga & Wei Shi & Shoukat Afshar-Sterle & Moritz F. Eissmann & Ashleigh R. Poh & Bhupinder Pal & Cyril Seillet & Richard M. Locksley &, 2023. "A tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Omid Omrani & Anna Krepelova & Seyed Mohammad Mahdi Rasa & Dovydas Sirvinskas & Jing Lu & Francesco Annunziata & George Garside & Seerat Bajwa & Susanne Reinhardt & Lisa Adam & Sandra Käppel & Nadia D, 2023. "IFNγ-Stat1 axis drives aging-associated loss of intestinal tissue homeostasis and regeneration," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Xiangwei Li & Thomas Delerue & Ben Schöttker & Bernd Holleczek & Eva Grill & Annette Peters & Melanie Waldenberger & Barbara Thorand & Hermann Brenner, 2022. "Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    6. Ahrum Son & Hyunsoo Kim & Jolene K. Diedrich & Casimir Bamberger & Daniel B. McClatchy & Stuart A. Lipton & John R. Yates, 2024. "Using in vivo intact structure for system-wide quantitative analysis of changes in proteins," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Yasuhiko Haga & Yoshitaka Sakamoto & Keiko Kajiya & Hitomi Kawai & Miho Oka & Noriko Motoi & Masayuki Shirasawa & Masaya Yotsukura & Shun-Ichi Watanabe & Miyuki Arai & Junko Zenkoh & Kouya Shiraishi &, 2023. "Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Jialiang S. Wang & Tushar Kamath & Courtney M. Mazur & Fatemeh Mirzamohammadi & Daniel Rotter & Hironori Hojo & Christian D. Castro & Nicha Tokavanich & Rushi Patel & Nicolas Govea & Tetsuya Enishi & , 2021. "Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    9. Ryan J. Geusz & Allen Wang & Dieter K. Lam & Nicholas K. Vinckier & Konstantinos-Dionysios Alysandratos & David A. Roberts & Jinzhao Wang & Samy Kefalopoulou & Araceli Ramirez & Yunjiang Qiu & Joshua , 2021. "Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    10. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. Aftab Nadeem & Athar Alam & Eric Toh & Si Lhyam Myint & Zia ur Rehman & Tao Liu & Marta Bally & Anna Arnqvist & Hui Wang & Jun Zhu & Karina Persson & Bernt Eric Uhlin & Sun Nyunt Wai, 2021. "Phosphatidic acid-mediated binding and mammalian cell internalization of the Vibrio cholerae cytotoxin MakA," PLOS Pathogens, Public Library of Science, vol. 17(3), pages 1-34, March.
    12. Xingxing Ren & Qiuyuan Liu & Peirong Zhou & Tingyue Zhou & Decai Wang & Qiao Mei & Richard A. Flavell & Zhanju Liu & Mingsong Li & Wen Pan & Shu Zhu, 2024. "DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Hao A. Duong & Kenkichi Baba & Jason P. DeBruyne & Alec J. Davidson & Christopher Ehlen & Michael Powell & Gianluca Tosini, 2024. "Environmental circadian disruption re-writes liver circadian proteomes," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    14. Xuelong Yao & Zongyang Lu & Zhanying Feng & Lei Gao & Xin Zhou & Min Li & Suijuan Zhong & Qian Wu & Zhenbo Liu & Haofeng Zhang & Zeyuan Liu & Lizhi Yi & Tao Zhou & Xudong Zhao & Jun Zhang & Yong Wang , 2022. "Comparison of chromatin accessibility landscapes during early development of prefrontal cortex between rhesus macaque and human," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    15. Ramachandran Prakasam & Angela Bonadiman & Roberta Andreotti & Emanuela Zuccaro & Davide Dalfovo & Caterina Marchioretti & Debasmita Tripathy & Gianluca Petris & Eric N. Anderson & Alice Migazzi & Lau, 2023. "LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    16. Susanne Kessler & Bradly Burke & Geoffroy Andrieux & Jan Schinköthe & Lea Hamberger & Johannes Kacza & Shijun Zhan & Clara Reasoner & Taru S. Dutt & Maria Kaukab Osman & Marcela Henao-Tamayo & Julian , 2024. "Deciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    17. Li Guo & Cheng Hu & Yang Liu & Xiaoyu Chen & Deli Song & Runling Shen & Zhanzhen Liu & Xudong Jia & Qinfen Zhang & Yuanzhu Gao & Zhezhi Deng & Tao Zuo & Jun Hu & Wenbo Zhu & Jing Cai & Guangmei Yan & , 2023. "Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    18. Mijeong Kim & Yu Jin Jang & Muyoung Lee & Qingqing Guo & Albert J. Son & Nikita A. Kakkad & Abigail B. Roland & Bum-Kyu Lee & Jonghwan Kim, 2024. "The transcriptional regulatory network modulating human trophoblast stem cells to extravillous trophoblast differentiation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    19. Alejandro Gomez Toledo & Eleni Bratanis & Erika Velásquez & Sounak Chowdhury & Berit Olofsson & James T. Sorrentino & Christofer Karlsson & Nathan E. Lewis & Jeffrey D. Esko & Mattias Collin & Oonagh , 2023. "Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    20. Cecilia Pessoa Rodrigues & Aindrila Chatterjee & Meike Wiese & Thomas Stehle & Witold Szymanski & Maria Shvedunova & Asifa Akhtar, 2021. "Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice," Nature Communications, Nature, vol. 12(1), pages 1-21, 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:13:y:2022:i:1:d:10.1038_s41467-022-32846-4. 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.