小柯机器人

2019年8月20日，法国巴黎文理研究大学Olivier Lantz和Franois Legoux研究团队合作在《自然—免疫学》在线发表论文，报道了代谢特异T细胞谱系决定的分子机制。

研究人员使用单细胞RNA测序对5-OP-RU特异性胸腺细胞的发育路径进行了表征。除了在骨髓来源造血细胞上选择的已知MAIT1和MAIT17效应亚群外，研究人员还鉴定了在胸腺上皮细胞上选择并分化成CD44阴性初始T细胞的5-OP-RU特异性胸腺细胞。MAIT细胞阳性选择需要通过接头蛋白SAP发出信号，调控转录因子ZBTB16的表达。单细胞的拟时间排序揭示了在胸腺上皮细胞或造血细胞上选择的5-OP-RU特异性胸腺细胞的转录轨迹。这项研究中得到的模型描绘了T细胞的谱系决定。

据了解，粘膜相关恒定T细胞（MAIT细胞）能够识别由MHC Ib类分子MR1呈递的微生物代谢物5-OP-RU（5-(2-oxopropylideneamino)-6-D-ribitylaminouracil）。MAIT细胞在胸腺发育期间获得效应功能，但所涉及的机制尚不清楚。

附：英文原文

Title: Molecular mechanisms of lineage decisions in metabolite-specific T cells

Author: Franois Legoux, Jules Gilet, Emanuele Procopio, Klara Echasserieau, Karine Bernardeau, Olivier Lantz

Issue&Volume: 2019-08-20

Abstract: Mucosal-associated invariant T cells (MAIT cells) recognize the microbial metabolite 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) presented by the MHC class Ib molecule, MR1. MAIT cells acquire effector functions during thymic development, but the mechanisms involved are unclear. Here we used single-cell RNA-sequencing to characterize the developmental path of 5-OP-RU-specific thymocytes. In addition to the known MAIT1 and MAIT17 effector subsets selected on bone-marrow-derived hematopoietic cells, we identified 5-OP-RU-specific thymocytes that were selected on thymic epithelial cells and differentiated into CD44 naive T cells. MAIT cell positive selection required signaling through the adapter, SAP, that controlled the expression of the transcription factor, ZBTB16. Pseudotemporal ordering of single cells revealed transcriptional trajectories of 5-OP-RU-specific thymocytes selected on either thymic epithelial cells or hematopoietic cells. The resulting model illustrates T cell lineage decisions.

DOI: 10.1038/s41590-019-0465-3

Source: https://www.nature.com/articles/s41590-019-0465-3

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex