gamma delta T cells in the pathogenesis of atherosclerosis

众所周知，动脉粥样硬化是一种慢性炎症性疾病，其中先天性和适应性免疫反应共同促进血管壁内的炎症过程。各种免疫细胞类型已被揭示有助于动脉粥样硬化病变发展的起始和进展。除了单核细胞/巨噬细胞和树突状细胞之外，促炎和抗炎T细胞应答之间的平衡及其通过调节机制的调节也是动脉粥样硬化的关键决定因素。特别是，已知Th 1应答发挥主要的促动脉粥样硬化作用，并被调节性T细胞抵消。Th 17细胞及其原型细胞因子IL-17在动脉粥样硬化中的作用仍存在争议。γ δ T细胞在动脉粥样硬化中的作用尚未评估。γ δ T细胞被认为是具有先天免疫细胞特征的非常规T细胞亚群。我们在这里将研究γ δ T细胞受体和模式识别受体在γ δ T细胞活化中的作用，并将研究它们在动脉粥样硬化形成中的作用。我们将进一步评估树突状细胞和γ δ T细胞之间的串扰，这些细胞在血管壁中形成免疫反应，特别关注IL-23/受体途径。我们将进一步尝试建立抗体介导的血管γ δ T细胞活化用于体内动脉粥样硬化保护的治疗策略。最后，我们将分析人类动脉粥样硬化中γ δ T细胞中细胞因子/受体和效应分子的表达，从而建立我们的机制研究与人类疾病之间的联系，并为抗动脉粥样硬化治疗提供新的推定靶点。

It is well recognized that atherosclerosis is a chronic inflammatory disease in which both innate and adaptive immune responses cooperate to fuel the inflammatory process within the vascular wall. Various immune cell types have been revealed to contribute to the initiation and progression of atherosclerotic lesion development. Besides monocytes/macrophages and dendritic cells, also the balance between pro-inflammatory and anti-inflammatory T cell responses and their modulation by regulatory mechanisms is a critical determinant of atherosclerosis. In particular, Th1 responses are known to play a major pro-atherogenic role, and are counterbalanced by regulatory T cells. The role of Th17 cells and their prototypical cytokine IL-17 in atherosclerosis remain controversial. The role of gamma delta T cells in atherosclerosis has not been evaluated. Gamma delta T cells are regarded as a non-conventional T cell subset endowed with features of innate immune cells. We here will study the role the gamma delta T cell receptor and pattern recognition receptors in the activation of gamma delta T cells, and will investigate their functional contribution to atherogenesis. We will furthermore evaluate the crosstalk between dendritic cells and gamma delta T cells that shape the immune response in the vascular wall with a particular focus on the IL-23/receptor pathway. We will furthermore attempt to establish a therapeutic strategy of antibody-mediated activation of vascular gamma delta T cells for atheroprotection in vivo. Finally, we will analyze the expression of cytokines/receptors and effector molecules identified in gamma delta T cells in human atherosclerosis, thus establishing a link between our mechanistic studies and human disease, and providing new putative targets for anti-atherosclerotic therapies.