Investigation of novel therapeutic approach through regulatory T cells (Tr) and dendritic cells (DCs) for the patients with autoimmune hepatitis (AIH)

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(1) Expression of toll-like receptor (TLR) family on Dendritic cells (DCs) in patients with autoimmune hepatitis (AIH). Total RNA was extracted from isolated T-reg and non-T-reg fractions and the amount of mRNA for TLR2, 3, 4, 6, 7, 8, 9were evaluated by real time PCR. TLR3, 6, 7, 9were expressed on circulating myeloid DC (MDC) and plasmacytoid DC (PDC) in controls, while only TLR6was expressed on those in patients with AIH. Thus different expression pattern of TLRs on DCs might have some influence on the pathogenesis of AIH.(2) Expression of apoptosis-related molecules on DCs, and susceptibility of DCs to apoptosis induced through TNF-R1 in patients with AIH.Total RNA was extracted from circulating myeloid DC (MDC) and plasmacytoid DC (PDC), the amount of mRNA for TNF-R1, TNF-RS18, Fas, Bcl-2, Bax, Bad, FAST, PKR, Apaf-1, and c-FLIP were evaluated by real time PCR. Further, after incubation of MDC+PDC in the presence of TNFα, susceptibility to apoptosis induced through TNF-R1 was evaluated by counting the number of apoptotic DCs. TNF-RS18, TNF-R1, Bad, and FAST were expressed on freshly isolated MDC and PDC both in AIH and control. However, expression of TNF-R1 and Bad was significantly suppressed in AIH compared with controls. After 72 hour incubation in the presence of TNFα, the amount of apoptotic MDC and PDC in controls increased from 30.0% to 45.8%, whereas that in AIH changed from 33.3% to 34.5%, suggesting the possibility that apoptosis of MDC and PDC induced by signals through TNF-R1 is suppressed in AIH.