| First Author | Barreau F | Year | 2010 |
| Journal | Gut | Volume | 59 |
| Issue | 2 | Pages | 207-17 |
| PubMed ID | 19837677 | Mgi Jnum | J:194143 |
| Mgi Id | MGI:5470387 | Doi | 10.1136/gut.2008.171546 |
| Citation | Barreau F, et al. (2010) Nod2 regulates the host response towards microflora by modulating T cell function and epithelial permeability in mouse Peyer's patches. Gut 59(2):207-17 |
| abstractText | 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 gamma (anti-IFNgamma) 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, IFNgamma and TNFalpha. 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. |
