title: Suppressive role of hepatic dendritic cells in concanavalin A-induced hepatitis.
abstract: Concanavalin A (Con A)-induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c+ I-A(low) B220+); however, conventional DC were CD11c+ I-A(high) B220(-). At an early stage (3-6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12-24 h) in parallel with hepatic failure. The hepatic CD11c+ DC population contained many CD11b(-) cells, while the majority of splenic CD11c+ DC were CD11b+. After Con A administration, the proportion of I-A+ and CD11b+ cells within the CD11c+ DC population tended to increase in the liver, but not in the spleen. Similarly, expression of the activation markers CD80, CD86 and CD40 by CD11c+ DC increased in the liver, but not in the spleen. Next, adoptive transfer of DC isolated from the liver and spleen was performed 3 h after Con A administration to examine the immunomodulatory function of DC. Only hepatic DC had the ability to suppress hepatic failure. Analysis of cytokine production and subsequent identification of the effector cells showed that hepatic DC achieved this by suppressing the production of interleukin (IL)-12 and IL-2, rather than modulating effector cell function.
authors: Department of Medical Technology, School of Health Sciences, Niigata University, Niigata, Japan. tomiyama@clg.niigata-u.ac.jp
authors: C
authors: C
authors: Tomiyama
authors: H
authors: H
authors: Watanabe
authors: Y
authors: Y
authors: Izutsu
authors: M
authors: M
authors: Watanabe
authors: T
authors: T
authors: Abo
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D039481:CD11b Antigen / Q000096:biosynthesis / Q000276:immunology; D039521:CD11c Antigen / Q000096:biosynthesis / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis; D003208:Concanavalin A / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D019693:Hepatitis, Autoimmune / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018664:Interleukin-12 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008099:Liver / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039481:CD11b Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; D007376:Interleukin-2; D003208:Concanavalin A; D018664:Interleukin-12