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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Mucosal Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1402834

Sirtuin 6 inhibits group 3 innate lymphoid cells function and gut immunity by suppressing IL-22 production

Provisionally accepted
Xiaohui Su Xiaohui Su 1,2,3Linfeng Zhao Linfeng Zhao 1,2,3Huasheng Zhang Huasheng Zhang 1,2,3Dongdi Wang Dongdi Wang 1,2,3Lei Shen Lei Shen 1,2,3*
  • 1 Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 2 Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 3 Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai, China

The final, formatted version of the article will be published soon.

    Group 3 innate lymphoid cells (ILC3s) express the transcription factor RORt and produce cytokines IL-22 and IL-17. They are enriched in the intestinal mucosa and play important roles in host defense against infection and inflammatory diseases. Sirtuin 6 (SIRT6) is a nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase and has been shown to control intestinal epithelial cell differentiation and survival. However, the role of SIRT6 in ILC3s remains unknown. Here, we show that SIRT6 inhibits IL-22 expression in intestinal ILC3s in a cell-intrinsic manner. Deletion of SIRT6 in ILC3s does not affect the cell numbers of total ILC3s and subsets, but results in increased IL-22 production. Furthermore, ablation of SIRT6 in ILC3s protects mice against Citrobacter rodentium infection and dextran sodium sulfate-induced colitis. Our results suggest that SIRT6 may play a role in ILC3 function by regulating gut immune responses against bacterial infection and inflammation.

    Keywords: Sirtuin 61, Group 3 innate lymphoid cells2, IL-223, Gut immunity4, inflammation5

    Received: 18 Mar 2024; Accepted: 08 Aug 2024.

    Copyright: © 2024 Su, Zhao, Zhang, Wang and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Lei Shen, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.