A role for vimentin in Crohn disease

Abstract

Crohn disease (CD), one of the major chronic inflammatory bowel diseases, occurs anywhere in the gastrointestinal tract with discontinuous transmural inflammation. A number of studies have now demonstrated that genetic predisposition, environmental influences and a dysregulated immune response to the intestinal microflora are involved. Major CD susceptibility pathways uncovered through genome-wide association studies strongly implicate the innate immune response (NOD2), in addition to the more specific acquired T cell response (IL23R, ICOSLG) and autophagy (ATG16L1, IRGM). Examination of the disease-associated microbiome, although complex, has identified several potentially contributory microorganisms, most notably adherent-invasive E.coli strains (AIEC), which have been isolated by independent investigators in both adult and pediatric CD patients. Here we discuss our recent finding that the type-III intermediate filament (IF) protein VIM/vimentin is a novel NOD2 interacting protein that regulates NOD2 activities including inflammatory NFKB1 signaling, autophagy and bacterial handling.

Keywords: AIEC; Crohn disease; NOD2; autophagy; vimentin.

Figure 1. Proposed interaction of VIM, NOD2 and the autophagy pathway during the invasion of host cells by AIEC. VIM expressed on the surface of host cells acts as a receptor for AIEC. The interaction of VIM and NOD2 at the plasma membrane allows NOD2 to engage with pathogens and signal an appropriate inflammatory response (through NFKB1) and antimicrobial response (through recruitment of ATG16L1). Internalized pathogens are trafficked along the cytoskeletal network via the autophagy pathway to lysosomes for degradation.