http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100319/-/DC1.

Background & Aims-The commensal microbiota is believed to have an important role in regulating immune responsiveness and preventing intestinal inflammation. Intestinal microbes produce signals that regulate inflammation via Toll-like receptor (TLR) signaling, but the mechanisms of this process are poorly understood. We investigated the role of the anti-inflammatory cytokine, IL-10, in this signaling pathway using a mouse model of colitis.

SUMMARYPatients with chronic hepatitis C (CHC) are unable to prime and maintain vigorous T cell responses that are initiated during the acute phase of hepatitis C virus (HCV) infection. As dendritic cells (DCs) induce and regulate both innate and adaptive immune responses, the aim of this study was to analyse two critical functions of DCs: firstly, production of interferon (IFN)-a and, secondly, polarization of T helper 1 lymphocytes. The frequencies of plasmacytoid DC (PDC) and myeloid DC (MDC) were estimated in 63 patients with CHC and 34 normal controls using four-colour flow cytometry. Circulating DCs were isolated from peripheral blood of CHC patients ( n = 10) and normal controls ( n = 10). These DCs were cultured with herpes simplex virus-1 to evaluate their capacity to produce IFN-a . The capacity of DCs to induce polarization of autologous naive CD4 + T lymphocytes to IFN-g -producing effector T lymphocytes was also assessed. The frequencies of PDCs producing intracellular IFN-a ( P < 0·01) and the levels of IFN-a in culture supernatant of PDCs ( P < 0·01) were significantly lower in patients with CHC compared to those of normal controls. The numbers of MDC were significantly lower in patients with CHC (8·2 (6·0)/ m l, median (interquartile range), n = 63) compared to normal control (11·7 (7·8)/ m l, n = 34) ( P < 0·01). Moreover, DCs from patients with CHC induced significantly lower numbers of IFNg -producing effector T lymphocytes compared to that of controls ( P < 0·01). This study indicates that the low IFN-a -producing capacity and impaired T helper 1 polarization ability of DCs from patients with CHC might be responsible for the typical low anti-HCV immune responses in these patients.

These data suggest a role of MIF in the pathogenesis of UC. MIF may be used as a marker of disease activity in UC and control of MIF production may have therapeutic implications.