The nucleotide-binding oligomerisation protein 2 (NOD2) is a sensor for bacterial muramyl dipeptide, which ensures ileal expression of antimicrobial peptides (so-called α-defensins) and promotes cytokine and chemokine production by immunocytes and enterocytes. Defective NOD2 signaling pathway and impaired expression of defensins were inextricably linked to the pathogenesis of Crohn's disease, a common form of inflammatory bowel disease. NOD2 and defensin deficiency at the level of the epithelial barrier and gut-associated lymphoid tissue may favour Crohn's disease by failing to protect from enteropathogens and to instruct adaptive immune response in the gut micro-environment. Herein, we provide an overview on the key role of NOD2 and defensins in antigen-presenting function of dendritic cells and antigen-specific immunity. We also outline the urgent need for a better understanding of the regulators of NOD2 function and defensin biogenesis to support the development of a rational immunostimulatory treatment for restoring long-lasting immunity in Crohn's disease.
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