• Source: NLRC5

NLRC5, short for NOD-like receptor family CARD domain containing 5, is an intracellular protein that plays a role in the immune system. NLRC5 is a pattern recognition receptor implicated in innate immunity to viruses potentially by regulating interferon activity. It also acts as an innate immune sensor to drive inflammatory cell death, PANoptosis. In humans, the NLRC5 protein is encoded by the NLRC5 gene. It has also been called NOD27, NOD4, and CLR16.1.




Structure


Structurally, NLRC5 has a putative caspase recruitment domain (CARD), followed by a NACHT domain, and a C-terminal leucine-rich repeat (LRR) region.




Function


Through its structural features, NLRC5 acts as a key regulator of Major Histocompatibility Class I (MHCI) molecule expression, playing a significant role in the adaptive immune system. This aspect of NLRC5 function was further investigated with the help of Nlrc5-deficient mice, which showed reduced MHCI expression in lymphocytes (particularly T, NK and NKT lymphocytes). In lymphocytes, NLRC5 localizes to the nucleus and drives MHCI gene expression by occupying H-2D and H-2K gene promoters.
NLRC5 also functions as an innate immune sensor that, upon NAD+ depletion, forms a PANoptosome, driving PANoptosis and inflammation. PANoptosis is a prominent innate immune, inflammatory, and lytic cell death pathway initiated by innate immune sensors and driven by caspases and receptor-interacting protein kinases (RIPKs) through PANoptosomes. PANoptosomes are multi-protein complexes assembled by germline-encoded pattern-recognition receptor(s) (PRRs) (innate immune sensor(s)) in response to pathogens, including bacterial, viral, and fungal infections, as well as pathogen-associated molecular patterns, damage-associated molecular patterns, cytokines, and homeostatic changes during infections, inflammatory conditions, and cancer. NLRC5 forms a PANoptosome complex with other NLRs, including NLRP12 and NLRP3, in response to NAD+ depletion, driving PANoptosis via caspase-8 and RIPK3. Deletion of Nlrc5 protects mice from lethality in hemolytic, hemophagocytic lymphohistiocytosis, and colitis models.




References

Kata Kunci Pencarian:

• NLRC5
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• PANoptosis
• NOD-like receptor
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