. Author manuscript; available in PMC: 2012 Jan 22.

Published in final edited form as: J Mol Med (Berl). 2011 Aug 23;90(1):15–24. doi: 10.1007/s00109-011-0802-y

Table.

Possible mechanistic hypotheses of Nod2-associated CD pathogenesis

Hypothesis	Phenotypes	Reference
“Gain-of-function” Nod2 mutation	MDP stimulation of macrophages from Nod2^2939iC mutant mice resulted in increased NF-κB and IL-1β secretions when compared to those of wild-type mice. Oral treatment of Nod2^2939iC mutant mice with dextran sodium sulfate (DSS), showed increased IL-1β and inflammation in the colon compared to wild-type mice.	[66]
Nod2, negative regulator of TLR2 signaling	Splenic macrophages from Nod2 deficient mice produced increased levels of IL-12 upon TLR2 stimulation through activation of the NF-κB subunit c-Rel.	[71, 73]
Nod2 mutation leads to Impaired Paneth cell function	NOD2 mutations affect the expression of small anti- bacterial peptides from Paneth cells, increasing susceptibility to abnormal infection and inflammation in the gut.	[74, 81, 82]
Nod2 mutations lead to the suppression of IL-10 expression	3020insC Nod2 protein actively inhibits IL-10 transcription by blocking the phosphorylation of ribonucleoprotein hnRNP-A1 via the mitogen activated protein kinase p38.	[87]
Nod2 mediated autophagy	Nod2 directly interact with ATG16L1 for its recruitment at the site of bacterial entry, induce autophagy and regulates bacterial clearance.	[89–91]