Immunosuppressive effect of a non-proteinogenic amino acid from Srreptomyces through inhibiting allogeneic T cell proliferation.
Immunosuppressive effect of a non-proteinogenic amino acid from Srreptomyces through inhibiting allogeneic T cell proliferation.
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Srreptomyces 的非蛋白氨基酸通过抑制同种异体 T 细胞增殖发挥免疫抑制作用。
DOI：
10.1080/09168451.2019.1591262
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Nishiyama C
中科院分区：
文献类型：
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作者：
Yashiro T;Sakata F;Sekimoto T;Shirai T;Hasebe F;Matsuda K;Kurosawa S;Suzuki S;Nagata K;Kasakura K;Nishiyama M;Nishiyama C
肉豆蔻素（ISP-1）是fingolimod （FTY720）的先导化合物，其免疫抑制活性来源于其2-氨基-1,3-丙二醇结构。含有这种结构的非蛋白氨基酸(2S,6R)-二氨基-(5R,7)-二羟基庚酸（DADH），最近被鉴定为二肽次级代谢物vazabitide A， inStreptmycessp的生物合成中间体。沉没60404;然而，其对适应性免疫的影响尚未得到研究。在这项研究中，我们使用小鼠骨髓来源的树突状细胞（bmdc）和同种异体脾T细胞检测了DADH是否抑制混合淋巴细胞反应。虽然与ISP-1不同，DADH不抑制CD3和CD28交联诱导的T细胞增殖，但与DADH而非ISP-1预孵育的BMDCs显著降低了异体CD8+T细胞的扩增。基于这些结果，我们得出结论，DADH通过靶向dc抑制dc介导的T细胞活化。
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, inStreptmycessp. 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.