NOD2 and defensins: translating innate to adaptive immunity in Crohn's disease.
The nucleotide-binding oligomerisation protein 2 (NOD2) is a sensor for bacterial muramyl dipeptide, which ensures ileal expression of antimicrobial peptides (so-called alpha-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.
Peyrin-Biroulet
Laurent
L
INSERM, U795, Lille, France.
Chamaillard
Mathias
M
D017951:Antigen Presentation; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology*; D023082:Defensins / Q000235:genetics* / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D018448:Models, Immunological; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010581:Peyer's Patches / Q000276:immunology
D023082:Defensins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein