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IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans
Open accessAbstract
Significance: Chronic granulomatous disease (CGD) has an immunodeficiency component and, in addition, an autoinflammatory component in which autophagy and inflammasome activation are linked and amenable to IL-1 blockade. This study provides a rationale to perform clinical trials to investigate the efficacy of blocking IL-1 in CGD colitis and expands the therapeutic potential of IL-1 antagonists to inflammatory diseases with defective autophagy.
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“Notably, activation of LAP in macrophages also regulates inflammatory signaling pathways (258, 259).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [258]
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Metadata
- Authors
- de Luca, A., Smeekens, S. P., Casagrande, A., Iannitti, R., Conway, K. L., Gresnigt, M. S., Begun, J., Plantinga, T. S., Joosten, L. A. B., van der Meer, J. W. M., Chamilos, G., Netea, M. G., Xavier, R. J., Dinarello, C. A., Romani, L., & van de Veerdonk, F. L.
- Affiliations
- Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy;
- Radboud University Medical Center (NL)
- University of Perugia (IT)
- Harvard University (US)
- Department of Medicine, Radboud University Medical Centre, 6500 HB, Nijmegen, The Netherlands;
- University of Crete (GR)
- Corresponding author
- Dinarello, Charles A.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-02-18
- Volume
- 111
- Issue
- 9
- Pages
- 3526-3531
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3948220
- OpenAlex
- W2153164696
- Cited by
- 313
- References
- 49
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 10 · 2023: 16 · 2022: 22 · 2021: 32 · 2020: 24 · 2019: 34 · 2018: 26 · 2017: 41 · 2016: 35 · 2015: 26 · 2014: 18
- FWCI
- 18.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Crohn's and Colitis Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI‑15614, AI-62773, R56AI015614, R01AI062773, R01AI015614)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK083756, DK-60049, DK 83756, R01DK097485, DK 43351, R01DK060049, P30DK043351)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- chronic granulomatous disease, IL-1 receptor blockade, anakinra, autophagy, inflammasome activation, IL-1β, NADPH oxidase deficiency, colitis, invasive aspergillosis, macrophages, monocytes, neutrophil recruitment, Th17 response, reactive oxygen species
- MeSH terms
- Animals, Anti-Inflammatory Agents, Aspergillus fumigatus, Autophagy, Colitis, Enzyme-Linked Immunosorbent Assay, Granulomatous Disease, Chronic, Humans, Mice, Inbred C57BL, Mice, Mutant Strains, Microtubule-Associated Proteins, Phagosomes, Receptors, Interleukin-1, Statistics, Nonparametric, NADPH Oxidases, Mice, Interleukin-1beta, Interleukin 1 Receptor Antagonist Protein, Real-Time Polymerase Chain Reaction
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