{Reference Type}: Journal Article
{Title}: Immunosuppressive effect of a non-proteinogenic amino acid from Streptomyces through inhibiting allogeneic T cell proliferation.
{Author}: Yashiro T;Sakata F;Sekimoto T;Shirai T;Hasebe F;Matsuda K;Kurosawa S;Suzuki S;Nagata K;Kasakura K;Nishiyama M;Nishiyama C;
{Journal}: Biosci Biotechnol Biochem
{Volume}: 83
{Issue}: 6
{Year}: Jun 2019
{Factor}: 2.337
{DOI}: 10.1080/09168451.2019.1591262
{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.