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Inflammasome Components NALP 1 and 3 Show Distinct but Separate Expression Profiles in Human Tissues Suggesting a Site-specific Role in the Inflammatory Response
Open accessAbstract
Several autoinflammatory disorders such as Muckle-Wells syndrome are characterized by mutations in the NALP3/cryopyrin gene. NALP3 and NALP1 proteins can assemble to inflammasomes that activate caspase-1, resulting in the processing of proinflammatory cytokines IL-1β and IL-18. The present study was designed to determine which cells and tissues express NALP1 and NALP3. Monoclonal antibodies were developed and their use revealed distinct distribution profiles of NALP1 and NALP3. Granulocytes, monocytes (very weakly), dendritic cells, and B and T cells all express NALP1 and NALP3. Highest levels of NALP1 are found in T cells and Langerhans cells. Furthermore, NALP1 is present in glandular epithelial structures such as stomach, gut, lung, and, surprisingly, in neurons and testis. In contrast to NALP1, NALP3 shows a more restricted tissue distribution with expression mainly in non-keratinizing epithelia in the oropharynx, esophagus, and ectocervix. Moreover, NALP3 expression is found in the urothelial layer in the bladder. Likewise, a difference in subcellular distribution between NALP1 and NALP3 is observed because NALP1 is localized mainly in the nucleus, whereas NALP3 is predominantly cytoplasmic. We propose that the presence of NALP3 in epithelial cells lining the oral and genital tracts allows the rapid sensing of invading pathogens, thereby triggering an innate immune response.
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“several studies have characterized inflammasomes in neurons (de Rivero Vaccari et al, 2009;Kummer et al, 2007), which are capable of producing IL-1β (de Rivero Vaccari et al, 2009).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Kummer et al, 2007
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“F or p er so na l u se o nl y. Table 1 (Continued ) NLR Commonly used nomenclature subfamilya human mouse Other names and aliases Structure IPAF/NAIP Ipaf Ipaf CARD12, CLAN, NLRC4 CARD-NACHT-LRR Ipaf CARD12, CLAN CARD-NACHT-LRR NAIP BIRC1 BIR3x-NACHT-LRR NAIPa Birc1a, NAIP1 BIR3x-NACHT-LRR NAIPb Birc1b, Naip-rs6, NAIP…”
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Metadata
- Authors
- Kummer, J. A., Broekhuizen, R., Everett, H., Agostini, L., Kuijk, L., Martinon, F., Bruggen, R. V., & Tschopp, J.
- Affiliations
- University Medical Center Utrecht (NL)
- University of Lausanne (CH)
- Corresponding author
- Tschopp, Jürg
- Venue
- Journal of Histochemistry & Cytochemistry
- Publisher
- SAGE Publications
- Published
- 2007-05
- Volume
- 55
- Issue
- 5
- Pages
- 443-452
- ISSN
- 0022-1554 (ISSN-L)
- 1551-5044
- OpenAlex
- W2043091577
- Cited by
- 531
- References
- 34
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 25 · 2023: 44 · 2022: 24 · 2021: 34 · 2020: 21 · 2019: 40 · 2018: 27 · 2017: 24 · 2016: 23 · 2015: 38 · 2014: 25 · 2013: 36 · 2012: 30
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Histochemistry & Cytochemistry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- NALP1, NLRP3, inflammasome, tissue distribution, autoinflammatory disease, Muckle-Wells syndrome, caspase-1, IL-1β, IL-18, Langerhans cells, epithelial cells, subcellular localization, innate immune response, mucosal immunity
- MeSH terms
- NLR Proteins, NLR Family, Pyrin Domain-Containing 3 Protein, Antibodies, Monoclonal, Carrier Proteins, Cell Line, Humans, Immunohistochemistry, Inflammation, Organ Specificity, Immunoblotting, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins
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