Article Text

Download PDFPDF
Nod2 regulates the host response towards microflora by modulating T cell function and epithelial permeability in mouse Peyer's patches


Nucleotide oligomerisation domain 2 (NOD2) mutations are associated with susceptibility to Crohn's disease and graft-versus-host disease, two human disorders related with dysfunctions of Peyer's patches (PPs). In Nod2−/− mice transcellular permeability and bacterial translocation are increased in PPs. In this study, we show that both anti-CD4+ and anti-interferon γ (anti-IFNγ) monoclonal antibodies abrogate this phenotype and reduce the expression of tumour necrosis factor (TNF) receptor 2 and the long isoform of myosin light chain kinase, thus demonstrating that immune T cells influence the epithelial functions. In turn, intraperitoneal injection of ML-7 (a myosin light chain kinase inhibitor) normalises the values of CD4+ T cells, IFNγ and TNFα. This reciprocal cross-talk is under the control of the gut microflora as shown by the normalisation of all parameters after antibiotic treatment. Toll-like receptor 2 (TLR2) and TLR4 expression were increased in Nod2−/− mice under basal conditions and TLR2 and TLR4 agonists induced an increased transcellular permeability in Nod2+/+ mice. Muramyldipeptide (a Nod2 agonist) or ML-7 was able to reverse this phenomenon. It thus appears that Nod2 modulates the cross-talk between CD4+ T cells and the epithelium recovering PP and that it downregulates the pro-inflammatory effect driven by the ileal microflora, likely by inhibiting the TLR pathways.

  • Nod2
  • Peyer's patch
  • MLCK
  • epithelial permeability
  • gut microflora
  • Crohn's disease
  • graft-versus-host disease
  • IBD
  • IBD basic research
  • immune response
  • CARD15
  • caspase recruitment domain 15
  • CD
  • Crohn's disease
  • DC
  • dendritic cell
  • FAE
  • follicle-associated epithelium
  • GALT
  • gut-associated lymphoid tissue
  • GVHD
  • graft-versus-host disease
  • LFs
  • lymphoid follicles
  • LPS
  • lipopolysaccharide
  • MDP
  • muramyl dipeptide
  • MLCK
  • myosin light chain kinase
  • NLRC2
  • natch Leucine-rich-repeat Card 2
  • NOD2
  • nucleotide oligomerisation domain 2
  • PGN
  • peptigoglycan
  • PP
  • Peyer's patches
  • Th1/2
  • T helper type 1/2
  • TLR
  • toll-like receptor
  • TNFR
  • TNF receptor

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles