关键词: DADH Dendritic cell ISP-1 T cell

Mesh : Amino Acids / pharmacology Animals Cell Proliferation / drug effects Heptanoic Acids / pharmacology Immunosuppressive Agents / pharmacology Lymphocyte Activation / drug effects Mice, Inbred BALB C Mice, Inbred C57BL Streptomyces / chemistry T-Lymphocytes / cytology drug effects

来  源:   DOI:10.1080/09168451.2019.1591262   PDF(Sci-hub)

Abstract:
The immunosuppressive activity of myriocin (ISP-1), a lead compound of fingolimod (FTY720), is derived from its 2-amino-1,3-propandiol structure. A non-proteinogenic amino acid, (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH), that contains this structure, was recently identified as a biosynthetic intermediate of a dipeptide secondary metabolite, vazabitide A, in Streptmyces sp. SANK 60404; however its effect on adaptive immunity has not yet been examined. In this study, we examined whether DADH suppresses mixed lymphocyte reaction using mouse bone marrow-derived dendritic cells (BMDCs) and allogeneic splenic T cells. Although T cell proliferation induced by cross-linking CD3 and CD28 were not suppressed by DADH unlike ISP-1, the pre-incubation of BMDCs with DADH but not ISP-1 significantly decreased allogeneic CD8+ T cell expansion. Based on these results, we concluded that DADH suppresses DC-mediated T cell activation by targeting DCs.
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