Myeloid OTULIN deficiency couples RIPK3-dependent cell death to Nlrp3 inflammasome activation and IL-1β secretion
- Author
- Maria Giulia Doglio, Lien Verboom, Emily Ruilova Sosoranga, Ulrika Frising (UGent) , Tomoko Asaoka (UGent) , Yannick Gansemans (UGent) , Filip Van Nieuwerburgh (UGent) , Geert van Loo (UGent) and Andy Wullaert (UGent)
- Organization
- Project
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- Characterizing the in vivo importance of OTULIN in liver through mouse gene targeting studies
- 3G0C4913
- Evaluating the function and the therapeutic potential of IFN-λ in intestinal carcinogenesis
- Going viral – how does murine norovirus alter intestinal immunity in the host and across generations?
- Dissecting cellular interactions underlying auto-inflammation in Familial Mediterranean Fever
- Investigating the effects of regulatory phosphorylation and linear ubiquitination on Pyrin-mediated auto-inflammatory disorders.
- Targeting the mevalonate pathway to treat inflammatory diseases
- Novel mechanisms of inflammation and cell death regulation in autoinflammatory and infectious diseases
- Investigating itaconic acid as a critical immunometabolite in Influenza and RSV infections
- Study of the molecular pathways through which linear (de)ubiquitination governs skin inflammation and aberrant epidermal stem cell activation
- Study of microbiota-host interactions during colon cancer development using a unique microbiome dependent mouse model
- Host-microbe interaction in intestinal homeostasis: unravelling the mechanisms involved in the onset of multiple inflammation-related diseases
- OTULIN in hepatocyte cell death and hepatocellular carcinoma
- Abstract
- Loss-of-function mutations in the deubiquitinase OTULIN result in an inflammatory pathology termed "OTULIN-related autoinflammatory syndrome" (ORAS). Genetic mouse models revealed essential roles for OTULIN in inflammatory and cell death signaling, but the mechanisms by which OTULIN deficiency connects cell death to inflammation remain unclear. Here, we identify OTULIN deficiency as a cellular condition that licenses RIPK3-mediated cell death in murine macrophages, leading to Nlrp3 inflammasome activation and subsequent IL-1β secretion. OTULIN deficiency uncoupled Nlrp3 inflammasome activation from gasdermin D-mediated pyroptosis, instead allowing RIPK3-dependent cell death to act as an Nlrp3 inflammasome activator and mechanism for IL-1β release. Accordingly, elevated serum IL-1β levels in myeloid-specific OTULIN-deficient mice were diminished by deleting either Ripk3 or Nlrp3. These findings identify OTULIN as an inhibitor of RIPK3-mediated IL-1β release in mice.
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HKMJVGN4GXV8GNSXB6J7RZHY
- MLA
- Doglio, Maria Giulia, et al. “Myeloid OTULIN Deficiency Couples RIPK3-Dependent Cell Death to Nlrp3 Inflammasome Activation and IL-1β Secretion.” SCIENCE IMMUNOLOGY, vol. 8, no. 89, 2023, doi:10.1126/sciimmunol.adf4404.
- APA
- Doglio, M. G., Verboom, L., Ruilova Sosoranga, E., Frising, U., Asaoka, T., Gansemans, Y., … Wullaert, A. (2023). Myeloid OTULIN deficiency couples RIPK3-dependent cell death to Nlrp3 inflammasome activation and IL-1β secretion. SCIENCE IMMUNOLOGY, 8(89). https://doi.org/10.1126/sciimmunol.adf4404
- Chicago author-date
- Doglio, Maria Giulia, Lien Verboom, Emily Ruilova Sosoranga, Ulrika Frising, Tomoko Asaoka, Yannick Gansemans, Filip Van Nieuwerburgh, Geert van Loo, and Andy Wullaert. 2023. “Myeloid OTULIN Deficiency Couples RIPK3-Dependent Cell Death to Nlrp3 Inflammasome Activation and IL-1β Secretion.” SCIENCE IMMUNOLOGY 8 (89). https://doi.org/10.1126/sciimmunol.adf4404.
- Chicago author-date (all authors)
- Doglio, Maria Giulia, Lien Verboom, Emily Ruilova Sosoranga, Ulrika Frising, Tomoko Asaoka, Yannick Gansemans, Filip Van Nieuwerburgh, Geert van Loo, and Andy Wullaert. 2023. “Myeloid OTULIN Deficiency Couples RIPK3-Dependent Cell Death to Nlrp3 Inflammasome Activation and IL-1β Secretion.” SCIENCE IMMUNOLOGY 8 (89). doi:10.1126/sciimmunol.adf4404.
- Vancouver
- 1.Doglio MG, Verboom L, Ruilova Sosoranga E, Frising U, Asaoka T, Gansemans Y, et al. Myeloid OTULIN deficiency couples RIPK3-dependent cell death to Nlrp3 inflammasome activation and IL-1β secretion. SCIENCE IMMUNOLOGY. 2023;8(89).
- IEEE
- [1]M. G. Doglio et al., “Myeloid OTULIN deficiency couples RIPK3-dependent cell death to Nlrp3 inflammasome activation and IL-1β secretion,” SCIENCE IMMUNOLOGY, vol. 8, no. 89, 2023.
@article{01HKMJVGN4GXV8GNSXB6J7RZHY,
abstract = {{Loss-of-function mutations in the deubiquitinase OTULIN result in an inflammatory pathology termed "OTULIN-related autoinflammatory syndrome" (ORAS). Genetic mouse models revealed essential roles for OTULIN in inflammatory and cell death signaling, but the mechanisms by which OTULIN deficiency connects cell death to inflammation remain unclear. Here, we identify OTULIN deficiency as a cellular condition that licenses RIPK3-mediated cell death in murine macrophages, leading to Nlrp3 inflammasome activation and subsequent IL-1β secretion. OTULIN deficiency uncoupled Nlrp3 inflammasome activation from gasdermin D-mediated pyroptosis, instead allowing RIPK3-dependent cell death to act as an Nlrp3 inflammasome activator and mechanism for IL-1β release. Accordingly, elevated serum IL-1β levels in myeloid-specific OTULIN-deficient mice were diminished by deleting either Ripk3 or Nlrp3. These findings identify OTULIN as an inhibitor of RIPK3-mediated IL-1β release in mice.}},
articleno = {{eadf4404}},
author = {{Doglio, Maria Giulia and Verboom, Lien and Ruilova Sosoranga, Emily and Frising, Ulrika and Asaoka, Tomoko and Gansemans, Yannick and Van Nieuwerburgh, Filip and van Loo, Geert and Wullaert, Andy}},
issn = {{2470-9468}},
journal = {{SCIENCE IMMUNOLOGY}},
language = {{eng}},
number = {{89}},
pages = {{17}},
title = {{Myeloid OTULIN deficiency couples RIPK3-dependent cell death to Nlrp3 inflammasome activation and IL-1β secretion}},
url = {{http://doi.org/10.1126/sciimmunol.adf4404}},
volume = {{8}},
year = {{2023}},
}
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