Dendritic cell control of T cell differentiation and immune responses by exosomes (B03)

树突状细胞通过外泌体控制 T 细胞分化和免疫反应 (B03)

• 批准号: 230013244
• 金额: --
• 依托单位: Forschungsbereich Immunologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/230013244?language=en
• 关键词: Dendritic; cell; control; differentiation; immune

Extracellular vesicles (EVs) are thought to modulate immune responses, although there is still little direct evidence in vivo for such a mechanism. Here we present a novel deep-learning-trained image analysis workflow that analyses cells which were stained in vivo with a chimeric eGFP-tagged Milk Fat Globule-EGF Factor 8 protein (MFG-E8-eGFP) to discriminate phosphatidylserine (PS)+ apoptotic cells from PS+ EVs. Using this analysis pipeline, we will analyze EVs in infected mice and human yellow fever vaccinees, with a focus on effector T cells and other cells which strongly bind PS+ EVs. These EVs are mostly exosomes of antigen-presenting cell origin as they carry MHC and costimulatory molecules able to drive T cell-fate decisions. Hence, our new tools allow us for the first time to evaluate in vivo data on the roles for exosomes as mediators of T cell differentiation and we will analyze if and how EVs influence the T cell compartment during infection and vaccination.

细胞外囊泡（EV）被认为是调节免疫反应，尽管在体内仍然很少有直接证据表明这种机制。在这里，我们提出了一种新的深度学习训练的图像分析工作流程，该工作流程分析了用嵌合eGFP标记的乳脂球-EGF因子8蛋白（MFG-E8-eGFP）在体内染色的细胞，以区分磷脂酰丝氨酸（PS）+凋亡细胞和PS+ EV。使用这个分析管道，我们将分析感染小鼠和人类黄热病疫苗接种者中的EV，重点是效应T细胞和其他强烈结合PS+ EV的细胞。这些EV主要是抗原呈递细胞来源的外泌体，因为它们携带能够驱动T细胞命运决定的MHC和共刺激分子。因此，我们的新工具使我们能够首次评估有关外泌体作为T细胞分化介体的作用的体内数据，我们将分析EV是否以及如何在感染和疫苗接种期间影响T细胞区室。