Impact of mitochondrial signaling and metabolic pathways on dendritic cell-mediated adaptive immunity

适应性免疫是通过包括树突状细胞和T淋巴细胞在内的特化免疫细胞的协同作用来实现的。激活后，两种类型的细胞都经历了主要的细胞类型特异性表型和功能变化，这涉及细胞代谢的深刻调整。目前，了解代谢途径如何影响免疫细胞功能仍然是一个重大挑战。线粒体是代谢的核心，因为它们提供基础和高度特异性细胞过程所需的能量和代谢物。然而，适应性免疫系统的细胞如何评估，维持和调整线粒体功能以响应激活刺激和病原体在很大程度上是未知的。在这个项目中，我们将研究线粒体信号成分和代谢适应如何有助于树突状细胞和T细胞的功能和可塑性。我们预见，拟议的研究可能会揭示免疫治疗设计的新方法，并可能为合理设计针对线粒体疾病的药物和疗法提供证据。

Adaptive immunity is achieved by the concerted action of specialized immune cells including dendritic cells and T lymphocytes. Following their activation, both types of cells undergo major cell-type-specific phenotypic and functional changes, which involve profound adjustments in cellular metabolism. Presently, it remains a major challenge to understand how metabolic pathways impact immune cell function. Mitochondria are central to metabolism as they provide the energy and metabolites required for basal and highly-specific cellular processes. Yet, how cells of the adaptive immune system evaluate, maintain and adjust mitochondrial function in response to activating stimuli and pathogens is largely unknown. In this project, we will investigate how mitochondrial signaling components and metabolic adaptations contribute to dendritic cell and T cell function and plasticity. We foresee that the proposed studies may reveal novel approaches in immunotherapy design and may provide evidence for the rational design of drugs and therapies against mitochondrial disease.