Cholera toxin B subunit linked to glutamic acid decarboxylase suppresses dendritic cell maturation and function.

摘要: Dendritic cells are the largest population of antigen presenting in body. One their main functions is to regulate delicate balance between immunity and tolerance responsible for maintenance immunological homeostasis. Disruption this often results chronic inflammation initiation organ specific autoimmune diseases such as rheumatoid arthritis, multiple sclerosis type I diabetes. The cholera toxin B subunit (CTB) a weak mucosal adjuvant known its ability stimulate antigenic proteins. However, conjugation CTB many autoantigens can induce resulting suppression autoimmunity. In study, we examined whether linkage 5kDa C-terminal protein fragment major diabetes autoantigen glutamic acid decarboxylase (GAD(35)), block dendritic cell (DC) biosynthesis co-stimulatory factor proteins CD86, CD83, CD80 CD40 secretion inflammatory cytokines. human umbilical cord blood monocyte-derived DC-GAD(35) incubation experiments showed that inoculation immature DCs (iDCs), with CTB-GAD(35) dramatically suppressed levels comparison GAD(35) alone inoculated iDCs. Surprisingly, iDCs presence CTB-autoantigen strong immunostimulatory molecules PMA Ionomycin revealed was capable arresting PMA+Ionomycin induced DC maturation. Consistent finding, mediated maturation accompanied by dramatic decrease pro-inflammatory cytokines IL-12/23p40 IL-6 significant increase immunosuppressive cytokine IL-10. Taken together, our experimental data suggest dominant 1 GAD strongly inhibits through down regulation factors biosynthesis. These emphasize possibility fusion enhance priming naive Th0 development direction T lymphocytes. phenomena observed here establish basis improvement augmented multi-component vaccine strategies complete organ-specific vivo.