Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion in vivo.
Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion in vivo.
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DOI：
10.3389/fimmu.2023.1109759
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发表时间：
2023
影响因子：
7.3
通讯作者：
Chen, Zhenjun
中科院分区：
文献类型：
--
作者：
Nelson, Adam G.;Wang, Huimeng;Dewar, Phoebe M.;Eddy, Eleanor M.;Li, Songyi;Lim, Xin Yi;Patton, Timothy;Zhou, Yuchen;Pediongco, Troi J.;Meehan, Lucy J.;Meehan, Bronwyn S.;Mak, Jeffrey Y. W.;Fairlie, David P.;Stent, Andrew W.;Kjer-Nielsen, Lars;Mccluskey, James;Eckle, Sidonia B. G.;Corbett, Alexandra J.;Souter, Michael N. T.;Chen, Zhenjun
粘膜相关不变T（MAIT）细胞是一群先天性T细胞，其通过识别由MHC-I相关蛋白1（MR 1）呈递的微生物核黄素合成衍生的代谢物抗原来介导宿主对微生物感染的免疫。即，有效的MAIT细胞抗原5-（2-氧代亚丙基氨基）-6-D-核糖基氨基尿嘧啶（5-OP-RU）和5-（2-氧代亚乙基氨基）-6-D-核糖基氨基尿嘧啶（5-OE-RU）通过核黄素前体5-氨基-6-D-核糖基氨基尿嘧啶（5-A-RU）分别与反应性羰基物质（RCS）甲基乙二醛（MG）和乙二醛（G）缩合形成。虽然MAIT细胞在人类中很丰富，但在小鼠中很少见，并且使用抗原和佐剂的扩增方案增加其丰度已被证明有助于在感染和疾病的小鼠模型中进行研究。 在这里，我们概述了三种方法来增加MAIT细胞的丰度在C57 BL/6小鼠使用炎症刺激，5-A-RU和MG的组合。我们的数据表明，合成5-A-RU与三种不同炎症刺激物之一的联合给药足以增加C57 BL/6小鼠中MAIT细胞的频率和绝对数量。所得到的增强MAIT细胞是功能性的，并且可以提供针对军团菌longbeachae的致死感染的保护。这些结果提供了在存在各种危险信号的情况下用高剂量的市售5-A-RU（± MG）扩增MAIT细胞的替代方法。
Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease. Here, we outline three methods to increase the abundance of MAIT cells in C57BL/6 mice using a combination of inflammatory stimuli, 5-A-RU and MG. Our data demonstrate that the administration of synthetic 5-A-RU in combination with one of three different inflammatory stimuli is sufficient to increase the frequency and absolute numbers of MAIT cells in C57BL/6 mice. The resultant boosted MAIT cells are functional and can provide protection against a lethal infection of Legionella longbeachae. These results provide alternative methods for expanding MAIT cells with high doses of commercially available 5-A-RU (± MG) in the presence of various danger signals.
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影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
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影响因子：
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作者：
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通讯作者：
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