P097 The efficacy of benzoxazole derivatives (B-98) as 5-lipooxygenase inhibitor and the change of T cell profiles in acute murine colitis model

Basic Science S47 MFI, p = 0.002), wereas GCSF-primed ROS production was unaffected (p = 0.79) indicating a specific GMCSF receptor signaling defect.E. coli uptake was not different, whereas a trend towards diminished killing was observed in C allele patients.In C-allele patients, GMCSF stimulation induced less activation of STAT3 (n = 5, 1.8±0.8vs 3.5±1.1 vs); AKT (11±5 vs 23±13) and ERK (30±20 vs 40±10) in C allele carriers.IL5 induced lower STAT5 (n = 4, 0.2±0.1 vs 0.5±0.2) and AKT signaling (0.03±0.06 vs 0.7±0.04).Conclusions: We show a specific defect in CSFR2B signaling in patients carrying the NCF4 risk allele.The CSFR2B receptor is used by both GMCSF and IL5, and both cytokines induce reduced signaling in C-allele patients.In contrast, priming of PMN by GCSF, which signals through a different receptor, was normal.Thus, the NCF4 risk allele confers a defect in CSFR2B signaling, and may identify a subset of CD patients whose inflammation is influenced by impaired innate immunity induced by neutrophils.GM-CSF treatment, which is beneficial for some patients, may be limited by NCF4 genetic background of patients.