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Transcription factor Tox2 is required for metabolic adaptation and tissue residency of ILC3 in the gut

  1. Author:
    Das, Arundhoti
    Martinez-Ruiz, Gustavo Ulises
    Bouladoux, Nicolas
    Stacy, Apollo
    Moraly, Josquin
    Vega-Sendino, Maria
    Zhao, Yongge
    Lavaert, Marieke
    Ding, Yi
    Morales-Sanchez, Abigail
    Harly, Christelle
    Seedhom, Mina O
    Chari,Raj
    Awasthi, Parirokh
    Ikeuchi, Tomoko
    Wang, Yueqiang
    Zhu, Jinfang
    Moutsopoulos, Niki M
    Chen, WanJun
    Yewdell, Jonathan W
    Shapiro, Virginia Smith
    Ruiz, Sergio
    Taylor, Naomi
    Belkaid, Yasmine
    Bhandoola, Avinash

  2. Author Address

    1Laboratory of Genome Integrity, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA. 2Laboratory of Genome Integrity, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA; Faculty of Medicine, Research Division, National Autonomous University of Mexico, Mexico City, Mexico; Children's Hospital of Mexico Federico Gomez, Mexico City, Mexico. 3Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, NIAID, NIH, Bethesda, MD, USA. 4Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, NIAID, NIH, Bethesda, MD, USA; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 5Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA. 6Laboratory of Genome Integrity, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA; Children's Hospital of Mexico Federico Gomez, Mexico City, Mexico. 7Université de Nantes, CNRS, Inserm, CRCINA, Nantes, France; LabEx IGO "Immunotherapy, Graft, Oncology," Nantes, France. 8Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, USA. 9Genome Modification Core, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. 10Mouse Modeling Core, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. 11Oral Immunity and Infection Section, NIDCR, NIH, Bethesda, MD, USA. 12Shenzhen Typhoon HealthCare, Shenzhen, Guangdong, China. 13Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA. 14Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD, USA. 15Department of Immunology, Mayo Clinic, Rochester, MN, USA. 16Laboratory of Genome Integrity, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA. Electronic address: avinash.bhandoola@nih.gov.
    1. Year: 2024
    2. Date: May 14
    3. Epub Date: 2024 04 18
  2. Journal: Immunity
    1. 57
    2. 5
    3. Pages: 1019-1036
  4. Type of Article: Article
  1. Abstract:

    Group 3 innate lymphoid cells (ILC3) are the major subset of gut-resident ILC with essential roles in infections and tissue repair, but how they adapt to the gut environment to maintain tissue residency is unclear. We report that Tox2 is critical for gut ILC3 maintenance and function. Gut ILC3 highly expressed Tox2, and depletion of Tox2 markedly decreased ILC3 in gut but not at central sites, resulting in defective control of Citrobacter rodentium infection. Single-cell transcriptional profiling revealed decreased expression of Hexokinase-2 in Tox2-deficient gut ILC3. Consistent with the requirement for hexokinases in glycolysis, Tox2-/- ILC3 displayed decreased ability to utilize glycolysis for protein translation. Ectopic expression of Hexokinase-2 rescued Tox2-/- gut ILC3 defects. Hypoxia and interleukin (IL)-17A each induced Tox2 expression in ILC3, suggesting a mechanism by which ILC3 adjusts to fluctuating environments by programming glycolytic metabolism. Our results reveal the requirement for Tox2 to support the metabolic adaptation of ILC3 within the gastrointestinal tract. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.immuni.2024.04.001
  3. PMID: 38677292
  4. PMCID: PMC11096055
  5. View record in Web of Science®
  6. WOS: 001243478700001
  7. PII : S1074-7613(24)00206-1

Library Notes

  1. Fiscal Year: FY2023-2024
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