Background: Breakdown of tolerance against the commensal microflora is believ ed to be a major factor in the pathogenesis of inflammatory bowel disease (IBD). Dendritic cells (DC) have been implicated in this process in various animal mod els, but data on human DC in IBD are very limited. Aim: To characterise plasmacy toid DC (PDC) and myeloid DC (MDC) in patients with active versus inactive IBD a nd healthy controls. Patients and Methods: Peripheral blood was obtained from 10 6 patients (Crohn’ s disease (CD) n = 49, ulcerative colitis (UC) n = 57) and h ealthy controls (n = 19). Disease activity was scored using themodified Truelove Witts (MTWSI) for UC and the Harvey Bradshaw severity indices (HBSI) for CD. Fo ur colour flow cytometric analysis was used to identify, enumerate, and phenotyp e DC. DC from patients with acute flare ups and healthy controls were cultured a nd stimulated with CpG ODN 2006 or lipopolysaccharide (LPS). Results: IBD patien ts in remission (PDC UC, 0.39% ; CD, 0.35% ; MDC- 1 UC, 0.23% ; CD, 0.22% of PBMC) have slightly lower numbers of circulating DC compared with healthy con trols (PDC 0.41% , MDC- 1 0.25% of PBMC). In acute flare ups IBD patients ex perience a significant drop of DC (PDC UC, 0.04% ; CD, 0.11% ; MDC- 1 UC, 0.1 1% ; CD, 0.14% of PBMC) that correlates with disease activity (correlation co efficients: PDC MTWSI, 0.93; HBSI, 0.79; MDC- 1 MTWSI, 0.75; HBSI, 0.81). Moreo ver, both express α l4β 7 integrin and display an immature phenotype. Freshly isolated PDC and MDC- 1 from untreated flaring IBD patients express higher base line levels of CD86 which increases further in culture and upon stimulation comp ared with healthy controls. Conclusion: IBD patients lack immature blood DC duri ng flare ups which possibly migrate to the gut. An aberrant response to microbia l surrogate stimuli suggests a disturbed interaction with commensals. Background: Breakdown of tolerance against the commensal microflora is believ ed to be a major factor in the pathogenesis of inflammatory bowel disease (IBD). Dendritic cells (DC) have been implicated in this process in various animal mod els, but data on human DC in IBD are very limited. Aim: To characterize plasmacytoid DC (PDC) and myeloid DC (MDC) in patients with active versus inactive IBD a nd healthy controls. Patients and Methods: Peripheral blood was obtained from 10 6 patients (Crohn’s Disease activity was scored using these modified Truelove Witts (MTWSI) for UC and the Harvey Bradshaw severity indices (HBSI) for (CD) n = 49, ulcerative colitis (UC) CD. Fo ur color flow cytometric analysis was used to identify, enumerate, and phenotyp e DC. DC from patients with acute flare ups and healthy controls were cultured a nd stimulated with CpG ODN 2006 or lipopolysaccharide (LPS). Results: IBD patien ts in remission (PDC UC, 0.39%; C D, 0.35%; MDC-1 UC, 0.23%; CD, 0.22% of PBMC) have slightly lower numbers of circulating DC compared with healthy con trols (PDC 0.41%, MDC- 1 0.25% of PBMC) The correlates with disease activity (correlation co efficients: PDC MTWSI, IBD patients ex perience a significant drop of DC (PDC UC, 0.04%; CD, 0.11%; MDC- 1 UC, 0.1 1%; CD, 0.93; HBSI, 0.79; MDC-1 MTWSI, 0.75; HBSI, 0.81). Moreo ver, both express αl4β7 integrin and display an immature phenotype. Freshly isolated PDC and MDC- 1 from untreated flaring IBD patients express higher base line levels of CD86 which increases further in culture and upon stimulation comp ared with healthy controls. Conclusion: IBD patients lack immature blood DC duri ng flare ups which possibly migrate to the gut. An aberrant response to microbia l surrogate stimuli suggests a disturbed interaction with commensals.