NOD2 regulation of Toll-like receptor responses and the pathogenesis of Crohn's disease

Abstract

NOD2 signalling can both positively and negatively regulate Toll-like receptor (TLR) responses. Previous studies have shown that lack of NOD2 signalling (in NOD2 knockout mice) leads to increased peptidoglycan induction of interleukin (IL)-12 via TLR2. Studies in this issue of Gut show that lack of NOD2 signalling (in patients with NOD2 mutations) leads to decreased CpG induction of tumour necrosis factor and IL-8 via TLR9. The first type of abnormality suggests that NOD2 mutations act by enhancing effector T cell function and the second that NOD2 mutations act by impairing regulatory T cell function. We weigh these possibilities.