NOD2 and inflammation: current insights

Abstract

The nucleotide-binding oligomerization domain (NOD) protein, NOD2, belonging to the intracellular NOD-like receptor family, detects conserved motifs in bacterial peptidoglycan and promotes their clearance through activation of a proinflammatory transcriptional program and other innate immune pathways, including autophagy and endoplasmic reticulum stress. An inactive form due to mutations or a constitutive high expression of NOD2 is associated with several inflammatory diseases, suggesting that balanced NOD2 signaling is critical for the maintenance of immune homeostasis. In this review, we discuss recent developments about the pathway and mechanisms of regulation of NOD2 and illustrate the principal functions of the gene, with particular emphasis on its central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation. Furthermore, we survey recent studies illustrating the role of NOD2 in several inflammatory diseases, in particular, inflammatory bowel disease, of which it is the main susceptibility gene.

Are Bacteria Infectious Pathogens in Hidradenitis Suppurativa? Debate at the Symposium for Hidradenitis Suppurativa Advances Meeting, November 2017

“…The g-secretase complex is involved in the Notch pathway, which is important for cell signaling, normal maturation of skin and hair follicle cells, and immune function. There may be other genetic factors that dictate exuberant or inadequate immune responses to cutaneous bacteria, such as NOD2 (Negroni et al, 2018). These findings support a hypothesis that microbes may be a secondary or opportunistic actor in the setting of a primary genetic/immune defect.…”

Gene variability in matrix metalloproteinases in patients with recurrent aphthous stomatitis

“…Furthermore, MMP16 helps to activate gelatinase MMP2, which plays a role in promoting inflammation by its action on interleukin‐1 beta or chemokines . Alternatively, RIPK2 represents an interaction partner of nucleotide‐binding oligomerization domain‐containing protein 2 (NOD2), mediating activation of NFκB and the mitogen‐activated kinases (MAPKs) resulting in transcription of proinflammatory genes and cell differentiation, proliferation, and apoptosis . Polymorphisms of both NOD2 and RIPK2 genes were linked to numerous inflammatory diseases including Crohn's disease with ulcers as one of its manifestations …”

Overlapping dermatologic diagnoses in severe Crohn’s disease with duel genetic mutations

“…is the strongest known genetic factor associated with CD, with a 2-4 fold increased risk of CD in heterozygous NOD mutations and a 20-40 fold increased risk in homozygous mutations. 3,5,6 The mechanisms of IBD in XIAP-deficient patients are probably similar to those with NOD2 risk alleles in CD. 3,5 To the best of our knowledge, this represents the first reported case of duel XIAP and NOD2 gene mutations.…”

“…3,5,6 The mechanisms of IBD in XIAP-deficient patients are probably similar to those with NOD2 risk alleles in CD. 3,5 To the best of our knowledge, this represents the first reported case of duel XIAP and NOD2 gene mutations. Due to our patient's severe CD, the oral zinc supplementation was not adequately absorbed, leading to acquired acrodermatitis enteropathica.…”

“…1 Blau syndrome, suggesting balanced NOD2 signaling is critical for the maintenance of immune homeostasis. 5,6 In fact, NOD2…”