Hyperexpression of NOD2 in intestinal mast cells of Crohn's disease patients: Preferential expression of inflammatory cell-recruiting molecules via NOD2 in mast cells

NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP) has been implicated as a key player in intestinal immune health and disease. Mast cells (MCs) have been reported to be increased in the gut of patients with inflammatory bowel disease. However, NOD2 expression and its role in human primary MCs are unknown. The number of NOD2+ intestinal MCs was significantly increased in the Crohn's disease (CD) specimens compared to Ulcerative colitis (UC) specimens and controls. IFN-γ upregulated NOD2 expression in MCs. CXCL10 and urokinase-type plasminogen activator (uPA) upregulation was specific to MCs activated by MDP compared to MCs activated by LPS and IgE/anti-IgE. MDP-induced upregulation of ICAM-1, VCAM-1, and uPA was specific to MCs compared to mononuclear cells. The number of CXCL10+NOD2+ intestinal MCs was significantly increased in the CD patients. Our results suggest that NOD2+ MCs have specific pathogenic roles that involve the recruitment of inflammatory cells in CD.