NOD2

NOD2 is a protein that in humans is encoded by the NOD2 gene. It is a member of the NOD-like receptor (NLR) family, which plays a crucial role in the immune system by recognizing molecules derived from pathogens and initiating an immune response.

Function

NOD2 is an intracellular pattern recognition receptor that can detect bacterial peptidoglycan, specifically muramyl dipeptide (MDP). Upon recognition of MDP, NOD2 activates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, leading to the production of pro-inflammatory cytokines and chemokines. This process is essential for the body's defense against bacterial infections.

Clinical significance

Mutations in the NOD2 gene are associated with several diseases, including Crohn's disease, Blau syndrome, and early-onset sarcoidosis. These diseases are characterized by chronic inflammation, suggesting a role for NOD2 in the regulation of inflammatory responses.

Crohn's disease

In Crohn's disease, certain mutations in the NOD2 gene increase the risk of developing the disease. These mutations result in a NOD2 protein that is less able to recognize MDP, leading to a reduced immune response to bacteria in the gut. This may contribute to the chronic inflammation seen in Crohn's disease.

Blau syndrome

Blau syndrome is a rare genetic disorder characterized by granulomatous arthritis, uveitis, and dermatitis. It is caused by mutations in the NOD2 gene that result in a constitutively active NOD2 protein, leading to continuous activation of the NF-κB pathway and chronic inflammation.

Sarcoidosis

Early-onset sarcoidosis is a rare form of sarcoidosis that begins in childhood. Like Blau syndrome, it is associated with mutations in the NOD2 gene that result in a constitutively active NOD2 protein.

See also

• Pattern recognition receptor
• Innate immune system
• Inflammatory bowel disease
• Autoinflammatory disease