DefinitionThis section has been translated automatically.
The NLRC4 gene (NLRC4 stands for "NLR Family CARD Domain Containing 4") is a protein coding gene located at chromosome 2p22.3.
General informationThis section has been translated automatically.
The NLRC4 gene encodes a member of the caspase recruitment domain-containing NLR family. Members of this family play an essential role in the innate immune response, which is activated in the presence of a wide range of pathogenic organisms, tissue damage, and other cellular stresses.
Related signaling pathways include the nucleotide-binding domain, leucine rich repeat-containing receptor (NLR), and nucleotide-binding oligomerization domain(NOD) signaling pathways.
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PathophysiologyThis section has been translated automatically.
The encoded NLRC4 protein forms a key component of the NLRC4 inflammasomes. NLRC4 expression is upregulated by proinflammatory stimuli such as TNFα, among others. NLRC4 inflammasome activation is primarily regulated at the posttranscriptional level. The two best described regulatory mechanisms are ligand binding and phosphorylation (NLRC4 inflammasome- see below Inflammasomes). Formation of the NLRC4 complex leads to activation of caspase-1, which promotes cytokine production and pyroptosis (see below Necroptosis) of macrophages. The NLRC4 inflammasome is also activated as part of the innate immune response of intracellular bacteria.
Clinical pictureThis section has been translated automatically.
Diseases associated with NLRC4 include.
- Familial cold-induced autoinflammatory syndrome 4 (OMIM: 616115)
- and
- autoinflammation with infantile enterocolitis (Periodic Fever-Infantile Enterocolitis-Autoinflammatory Syndrome; OMIM: 616050).
Note(s)This section has been translated automatically.
Upon discovery of NLRC4 (formerly designated IPAF), it became clear that the full-length protein was unable to activate CASP1(effector of the NLRC4 inflammasome). In contrast, expression of truncated versions of the protein that lacked the C-terminal series of leucine-rich repeats (LRRs) triggered CASP1 activation. This illustrates that NLRC4 activation is tightly regulated by transcriptional and posttranscriptional mechanisms. This prevents unregulated inflammatory signaling by this complex.
LiteratureThis section has been translated automatically.
- Andrade WA et al (2020) NLRC4 biology in immunity and inflammation. J Leukoc Biol 108:1117-1127.
- Bauer R et al (2020) The NAIP/NLRC4 inflammasome in infection and pathology. Mol Aspects Med 76:100863.
- Duncan JA et al (2018) The NLRC4 inflammasome. Immunol Rev 281:115-123.
