The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies
Open accessAbstract
The inflammasome is a cytoplasmic multiprotein complex that promotes proinflammatory cytokine maturation in response to host- and pathogen-derived signals. Missense mutations in cryopyrin (NLRP3) result in a hyperactive inflammasome that drives overproduction of the proinflammatory cytokines IL-1β and IL-18, leading to the cryopyrin-associated periodic syndromes (CAPS) disease spectrum. Mouse lines harboring CAPS-associated mutations in Nlrp3 have elevated levels of IL-1β and IL-18 and closely mimic human disease. To examine the role of inflammasome-driven IL-18 in murine CAPS, we bred Nlrp3 mutations onto an Il18r-null background. Deletion of Il18r resulted in partial phenotypic rescue that abolished skin and visceral disease in young mice and normalized serum cytokines to a greater extent than breeding to Il1r-null mice. Significant systemic inflammation developed in aging Nlrp3 mutant Il18r-null mice, indicating that IL-1 and IL-18 drive pathology at different stages of the disease process. Ongoing inflammation in double-cytokine knockout CAPS mice implicated a role for caspase-1-mediated pyroptosis and confirmed that CAPS is inflammasome dependent. Our results have important implications for patients with CAPS and residual disease, emphasizing the need to explore other NLRP3-mediated pathways and the potential for inflammasome-targeted therapy.
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Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity
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Cited by
Inflammasomes: mechanism of action, role in disease, and therapeutics
Guo, H., Callaway, J. B., & Ting, J. P.-Y. (2015) · Nature Medicine · doi:10.1038/nm.3893 · Cited by 3,340
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
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The interleukin-1 family: back to the future
Garlanda, C., Dinarello, C. A., & Mantovani, A. (2013) · Immunity · doi:10.1016/j.immuni.2013.11.010 · Cited by 1,945
Targeting the NLRP3 inflammasome in inflammatory diseases
Mangan, M. S. J., Olhava, E. J., Roush, W. R., Seidel, H. M., Glick, G. D., & Latz, E. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.97 · Cited by 1,885
NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria
Zhong, Z., Umemura, A., Sanchez-Lopez, E., Liang, S., Shalapour, S., Wong, J., He, F., Boassa, D., Perkins, G., Ali, S. R., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.057 · Cited by 1,197
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Metadata
- Authors
- Brydges, S. D., Broderick, L., McGeough, M. D., Pena, C. A., Mueller, J. L., & Hoffman, H. M.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-10-01
- Volume
- 123
- Issue
- 11
- Pages
- 4695-4705
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2123531771
- Cited by
- 229
- References
- 9
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- green
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- Brydges, S. D., Broderick, L., McGeough, M. D., Pena, C. A., Mueller, J. L., & Hoffman, H. M. (2013). Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies. Journal of Clinical Investigation. https://doi.org/10.1172/jci71543
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