Mo1794 Endogenous Colonic Hydrogen Sulfide Prevents Inflammatory Oxidation

Abstract

G A A b st ra ct s an important role in the homeostasis of PP in response to the microbiota. However, we do not know the respective roles of Nod2 in the epithelial and immune compartments of PP. Methods: To investigate the part of Nod2 in epithelial and immune compartments within PP, chimeric mice were developed by reconstituting sublethally irradiated wild-type (WT) mice with bone marrow (BM) stem cells from Nod2 Knockout mice (KO) and vice versa. Three months following BM transplantation, paracellular permeability (FITC 4kD dextran flux) and E. coli translocation were assessed in Ussing chamber. The number of immune cells and cellular composition from PP of chimeric mice were determined by flow cytometry. Results: An excess of permeability and E. coli translocation was observed in PP of KO mice reconstituted by BM of KO mice (KO→KO) compared to WT mice reconstituted by BM WT mice (WT→WT). Permeability and E. coli translocation were also higher in PP from chimeric mice that did not express Nod2 in the immune compartment but expressed it in epithelial cells (KO→WT). These excesses of permeability and translocation in PP were comparable to Nod2 Knockout mice (KO→KO). Conversely, permeability and E. coli translocation from chimeric mice expressing Nod2 in immune cells but not in epithelial cells (WT→KO) were similar to controls. An excess of CD3+ T-cells but a decreased number of dendritic cells were observed in the PP from chimeric mice that did not express Nod2 in immune cells (KO→KO and KO→WT). Conclusion: Nod2 deficiency in the immune compartment is sufficient to alter the cellular composition of PP and the functionality of the follicle associated epithelium. These results highlight the importance of Nod2 in the dialogue between the immune and epithelial cells and may contribute to understand CD mechanisms.