hmgb在早期胰岛移植物丢失中的作用.pptVIP

HMGB在早期胰岛移植物丢失中的作用; ● major obstacle facing islet transplantation and hampersits clinical application: early loss of transplanted islets → the low efficiency of islet transplantation ● loss?of?transplanted?islets?is caused?by?NKT?cell–dependent?IFN-γ?production?by?Gr-1+CD11b+?cells ● ? in?the?activation?of?NKT?cells?and? Gr-1+CD11b+ ?cells?in?the?early?loss?of?transplanted?islets?remains?to?be?solved. ;High-mobility?group?box?1 (HMGB1) protein:?DNA-binding?protein? present?in?almost?all?eukaryotic?cells. HMGB1 stabilizes?nucleosome?formation?and?acts?as?a?nuclear? factor? that? enhances? transcription? HMGB1 play?crucial?roles?in?response?to?tissue?damage, is secreted?by?activated?immune?cells,?including?macrophages,?DCs,?and?NK? cells HMGB1?induces inflammatory?responses?by?transduction?of?cellular?signals?through?its?receptors,?such?as?TLR2,?TLR4 and?receptor?for?advanced?glycation?end?products? (RAGE) ;Involvement of HMGB1 in early loss of transplanted islets;IFN-γproduction of NKT cells and Gr-1+CD11b+ cells in the liver receiving islets is inhibited by anti-HMGB1 antibody;NKT cell–dependent IFN-γ production by Gr-1+CD11b+ cells upon stimulation with HMGB1. ;Involvement of TLR2 and RAGE but not TLR4 in HMGB1-dependent early loss of transplanted islets. ;Pancreatic islet cells are a major source of HMGB1, which mediates IFN-γ production by NKT cells and Gr-1+CD11b+ cells. ?;Cell types responsible for HMGB1-mediated cytokine production.;;;Islet?cells?themselves?are?a?major?source?of?HMGB1,?which?is?released?from?transplanted?islets.?Since?the?plasma?levels?of?HMGB1?reflect?the?degree?of?islet?damage,?HMGB1?could?be?a?marker?to?predict?rejection?of?transplanted?islets.? HMGB1?stimulates?production?of?inflammatory?cytokines? including?IL-12?and?IFN-γ?in?concert?with?DCs,?NKT?cells,?and?Neu?in?the?liver?receiving?islets.? These?inflammatory?cytokines?accelerated?the?injuries?of? transpl