ArticleImmunity2025
Gasdermin C cleavage by Cathepsin S modulates Rab7 vesicles in intestinal epithelial cells to amplify anti-helminth immunity.
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Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6citing papers in PubMed
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Who cites it
6 citing papers in PubMed.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Theme and variations: activation and regulation of gasdermin-mediated inflammation.Biochemical Society transactions · 2026Review
- CTSS regulates macrophage lipid metabolic reprogramming and white matter repair after intracerebral hemorrhage.Journal of translational medicine · 2026Article
- Article
- A novel PCOS susceptibility gene, cathepsin B, might be likely to contribute to the pyroptosis of ovarian granulosa cells.Journal of assisted reproduction and genetics · 2026Article
- Gasdermins in neurodegeneration: emerging mechanisms and therapeutic targets.Cell death & disease · 2025Review
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Authors and funding
28 authors.
Surya P PandeyDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Donghui YangDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA; School of Medicine, Tsinghua University, Beijing, China.
Lee HeddenDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Colin R LaughlinDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Weihong WangDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Ariadna S SotoDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Halah WinnerDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Luzmariel Medina SanchezDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Edith E CampanaDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Clarisse EnglDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Yanlin ZengDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; School of Medicine, Tsinghua University, Beijing, China.
Mohit RanaDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Lauren Van Der KraakDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mackenzie J BenderDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Joshua ProkopecDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Julia M FerrickDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Xinan MengInternational Biomedicine-X Research Center of the Second Affiliated Hospital, Zhejiang University School of Medicine, and the Zhejiang University, University of Edinburgh Institute, Haining 314400, Zhejiang, China.
Erica FongHealth Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
Mai SunHealth Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
Steven J MullettHealth Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Matthew MacDonaldHealth Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Stacy L GelhausHealth Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Simon C WatkinsDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Marlies MeiselDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Jakob von MoltkeDepartment of Immunology, University of Washington School of Medicine, Seattle, WA, USA.
Suhong XuInternational Biomedicine-X Research Center of the Second Affiliated Hospital, Zhejiang University School of Medicine, and the Zhejiang University, University of Edinburgh Institute, Haining 314400, Zhejiang, China.
Yi-Nan GongDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: yngong@pitt.edu.
Reinhard HinterleitnerDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA. Electronic address: reinhard@pitt.edu.
Funding
VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0MAutoimmunity and Immunopathology Training ProgramT32AI089443 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHLOMCHIK, MARK J · 2010 to 2024
$6.6MTuft cell effector functions in the small intestineR01AI145848 · NIAID · UNIVERSITY OF WASHINGTON · PI VON MOLTKE, JAKOB H. · 2020 to 2024
$2.8MRegulation of the tuft-ILC2 circuit in the small intestineR01AI167923 · NIAID · UNIVERSITY OF WASHINGTON · PI Jakob H. von Moltke · 2022 to 2026
$2.8MNecrotic survivors and plasma membrane integrity signalingDP2GM146320 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GONG, YI-NAN · 2021 to 2024
$2.3MRole of gut protists in celiac diseaseR01AI168478 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Reinhard Hinterleitner · 2023 to 2026
$2.3MSystemic immunoregulatory consequences of bacterial translocation during health and diseaseR01DK130897 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MEISEL, MARLIES · 2021 to 2025
$2.2MTuft Cell Effector Functions in the IntestineR37AI145848 · NIAID · UNIVERSITY OF WASHINGTON · PI Jakob H. von Moltke · 2025 to 2026
$1.4MDefining mechanisms of how immune checkpoint inhibitor-associated bacteria modulate tumor immunity in cancerR01CA293654 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Marlies Meisel · 2025 to 2026
$1.3MGut mucosal type-2 immunity to parasitic infectionsR21AI163721 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HINTERLEITNER, REINHARD · 2021 to 2022
$433kRole of Gut Protist Derived Compounds on Dietary Antigen Presenting Dendritic Cells in Celiac DiseaseF31DK138621 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MEDINA-SANCHEZ, LUZMARIEL · 2024 to 2024
$49kNCI NIH HHS P30 CA047904NCI NIH HHS R01 CA293654NIAID NIH HHS R01 AI145848NIAID NIH HHS R01 AI167923NIAID NIH HHS R01 AI168478NIAID NIH HHS R21 AI163721NIAID NIH HHS R37 AI145848NIAID NIH HHS T32 AI089443NIDDK NIH HHS F31 DK138621NIDDK NIH HHS R01 DK130897NIGMS NIH HHS DP2 GM146320
Abstract
Gasdermins are canonically associated with plasma membrane pore formation and lytic cell death. Gasdermin C (GsdmC), predominantly expressed in intestinal epithelial cells (IECs), seems to operate independently of these canonical roles. Here, we show that activated GsdmC is increased in response to type 2 immunity in the gut, driven by Cathepsin S (CTSS)-mediated cleavage. Although IEC cell death is not the main consequence of GsdmC cleavage, inserting a single amino acid (aa) within the lipid-binding motif to match that of the other gasdermins enhanced GsdmC oligomerization and increased GsdmC-mediated cell death. Mechanistically, instead of localizing to the plasma membrane, we showed that cleaved GsdmC targeted Rab7
Indexed as
CathepsinsEpithelial CellsHelminthsIntestinal Mucosarab GTP-Binding ProteinsAnimalsEndosomesHumansMiceMice, Inbred C57BLMice, Knockoutrab7 GTP-Binding Proteinscathepsin SCathepsinsrab7 GTP-Binding Proteinsrab7 GTP-binding proteins, mouserab GTP-Binding ProteinsCathepsin SGasdermin Chelminthintestinal epithelial cellsprotistRab7type 2 immune
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.