德国马克斯·普朗克免疫生物学和表观遗传学研究所Edward J. Pearce小组发现，浆细胞样树突细胞的活化依赖于不同氨基酸转运蛋白的协调表达。相关论文于2021年10月29日在线发表在《免疫》杂志上。

研究人员发现，白细胞介素-3（IL-3）诱导的Janus激酶2依赖性表达的SLC7A5和SLC3A2（包括大型中性氨基酸转运体）是哺乳动物雷帕霉素复合物1（mTORC1）营养传感器在应对toll样受体激动剂时激活的必要条件。这些氨基酸转运体的功能丧失协同阻止了浆细胞样树突状细胞（pDC）的细胞因子产生。

将体外激活的pDC与狼疮性肾炎病变的pDC进行比较，研究人员不仅发现SLC7A5、SLC3A2和SLC7A11，而且还发现外核苷酸焦磷酸酶-磷酸二酯酶2（ENPP2）是共同转录特征的组成部分，而且ENPP2的抑制也阻止了细胞因子的产生。这些数据为涉及到pDC的自身免疫性疾病确定了额外的治疗靶标。

据介绍，人类pDC是IL-3依赖性细胞，与自身免疫有关，但IL-3在pDC生物学中的作用却不甚明了。

附：英文原文

Title: Plasmacytoid dendritic cell activation is dependent on coordinated expression of distinct amino acid transporters

Author: Katarzyna M. Grzes, David E. Sanin, Agnieszka M. Kabat, Michal A. Stanczak, Joy Edwards-Hicks, Mai Matsushita, Alexandra Hackl, Fabian Hssler, Kristin Knoke, Sophie Zahalka, Matteo Villa, David M. Kofler, Reinhard E. Voll, Paola Zigrino, Mario Fabri, Erika L. Pearce, Edward J. Pearce

Issue&Volume: 2021-10-29

Abstract: Human plasmacytoid dendritic cells (pDCs) are interleukin-3 (IL-3)-dependent cellsimplicated in autoimmunity, but the role of IL-3 in pDC biology is poorly understood.We found that IL-3-induced Janus kinase 2-dependent expression of SLC7A5 and SLC3A2,which comprise the large neutral amino acid transporter, was required for mammaliantarget of rapamycin complex 1 (mTORC1) nutrient sensor activation in response to toll-likereceptor agonists. mTORC1 facilitated increased anabolic activity resulting in typeI interferon, tumor necrosis factor, and chemokine production and the expression ofthe cystine transporter SLC7A11. Loss of function of these amino acid transporterssynergistically blocked cytokine production by pDCs. Comparison of in vitro-activated pDCs with those from lupus nephritis lesions identified not only SLC7A5,SLC3A2, and SLC7A11 but also ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2)as components of a shared transcriptional signature, and ENPP2 inhibition also blockedcytokine production. Our data identify additional therapeutic targets for autoimmunediseases in which pDCs are implicated.

DOI: 10.1016/j.immuni.2021.10.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00446-5