Role of the aryl hydrocarbon receptor in immunosurveillant functions of murine dendritic epidermal T cells

皮肤是环境的屏障，含有免疫细胞，有助于对抗感染，伤口修复或消除癌细胞。在这个项目中，我们专注于一种特殊类型的免疫细胞，即所谓的树突状表皮T细胞（DETC）。在以前的工作中，我们发现配体激活的转录因子，芳烃受体（AHR）控制DETC的炎症相关基因的表达。我们现在想研究，这是否以及如何影响DETC的功能，如伤口修复，应激角质形成细胞的识别，或DETC对紫外线损伤的支持。从机制上讲，我们将研究AHR信号传导是否参与DETC活化后的代谢变化，即活化诱导的能量需求是否导致从优先氧化磷酸化到糖酵解的转变。此外，我们将分析表面受体CD69的参与，CD69是一种T细胞活化标志物，也是一种抑制炎症的分子，也是AHR信号传导的靶点。

The skin is a barrier to the environment and contains immune cells, which contribute to fighting infections, wound repair or elimination of cancer cells. In this project, we focus on a particular type of immune cells, the so-called dendritic epidermal T cells (DETC). In previous work we found that a ligand-activated transcription factor, the aryl hydrocarbon receptor (AHR) controls DETC´s expression of inflammation-related genes. We now want to study, whether and how this affects the functions of DETC, such as wound repair, recognition of stressed keratinocytes, or DETC´s support against UV-damage. Mechanistically, we will study whether AHR signaling is involved in DETC metabolic changes upon activation, i.e. whether the activation-induced energy needs result in shifts from preferential oxidative phosphorylation to glycolysis. Further, we will analyze the involvement of the surface receptor CD69, a T cell activation marker, but also a molecule inflammation dampening potential, and target of AHR-signaling.