NLRP3, NLRP6, and NLRP12 are inflammasomes with distinct expression patterns Article Swipe
Bo Wei
,
Zachary P. Billman
,
Kengo Nozaki
,
Helen S. Goodridge
,
Edward A. Miao
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.02.05.579000
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.02.05.579000
Inflammasomes are sensors that detect cytosolic microbial molecules or cellular damage, and in response they initiate a form of lytic regulated cell death called pyroptosis. Inflammasomes signal via homotypic protein-protein interactions where CARD or PYD domains are crucial for recruiting downstream partners. Here, we screened these domains from NLR family proteins, and found that the PYD domain of NLRP6 and NLRP12 could activate caspase-1 to induce cleavage of IL-1β and GSDMD. Inflammasome reconstitution verified that full length NLRP6 and NLRP12 formed inflammasomes in vitro, and NLRP6 was more prone to auto-activation. NLRP6 was highly expressed in intestinal epithelial cells (IEC), but not in immune cells. Molecular phylogeny analysis found that NLRP12 was closely related to NLRP3, but the activation mechanisms are different. NLRP3 was highly expressed in monocytes and macrophages, and was modestly but appreciably expressed in neutrophils. In contrast, NLRP12 was specifically expressed in neutrophils and eosinophils, but was not detectable in macrophages. NLRP12 mutations cause a periodic fever syndrome called NLRP12 autoinflammatory disease. We found that several of these patient mutations caused spontaneous activation of caspase-1 in vitro, which likely causes their autoinflammatory disease. Different cell types have unique cellular physiology and structures which could be perturbed by a pathogen, necessitating expression of distinct inflammasome sensors to monitor for signs of infection.
Related Topics
Concepts
Inflammasome
Pyroptosis
Pyrin domain
AIM2
Cell biology
NLRC4
Biology
Caspase 1
Caspase
Programmed cell death
NLRP1
Apoptosis
Chemistry
Inflammation
Immunology
Genetics
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.02.05.579000
- https://www.biorxiv.org/content/biorxiv/early/2024/02/08/2024.02.05.579000.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 60
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391636511
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4391636511Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2024.02.05.579000Digital Object Identifier
- Title
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NLRP3, NLRP6, and NLRP12 are inflammasomes with distinct expression patternsWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-02-08Full publication date if available
- Authors
-
Bo Wei, Zachary P. Billman, Kengo Nozaki, Helen S. Goodridge, Edward A. MiaoList of authors in order
- Landing page
-
https://doi.org/10.1101/2024.02.05.579000Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2024/02/08/2024.02.05.579000.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2024/02/08/2024.02.05.579000.full.pdfDirect OA link when available
- Concepts
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Inflammasome, Pyroptosis, Pyrin domain, AIM2, Cell biology, NLRC4, Biology, Caspase 1, Caspase, Programmed cell death, NLRP1, Apoptosis, Chemistry, Inflammation, Immunology, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1Per-year citation counts (last 5 years)
- References (count)
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60Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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