Prof. Dr. med. Andreas Habenicht

1 Atherosclerosis autoimmunity 动脉粥样硬化自身免疫

A fundamental unresolved issue in the pathogenesis of atherosclerosis is whether the advanced and clinically significant disease is associated with the generation of arterial wall-specific autoantigens recognized by autoimmune T cells or B cells. We have begun to isolate B-2 cells from diseased arteries, sequence their B cell receptors, clone and express the autoimmune antibodies and examine their role in atherosclerosis progression.

动脉粥样硬化发病机制中一个尚未解决的根本问题是，这种晚期且具有临床意义的疾病是否与自身免疫T细胞或B细胞识别的动脉壁特异性自身抗原的产生有关。我们已开始从患病动脉中分离B-2细胞，对其B细胞受体进行测序，克隆并表达自身免疫抗体，并研究其在动脉粥样硬化进展中的作用。

2 Tolerance dysfunction in atherosclerosis 动脉粥样硬化中的耐受性功能障碍

Tolerance dysfunction as a driver of atherosclerosis progression is poorly understood. Using single cell RNA sequencing coupled with T cell receptor or B cell receptor profiling, we aim to identify abnormal tolerance checkpoints as disease drivers.

耐受性功能障碍作为动脉粥样硬化进展的驱动因素尚不清楚。我们旨在利用单细胞RNA测序结合T细胞受体或B细胞受体分析，识别作为疾病驱动因素的异常耐受性检查点。

3 The impact of artery tertiary lymphoid organs (ATLOs) on atherosclerosis 动脉三级淋巴器官 (ATLO) 对动脉粥样硬化的影响

ATLOs belong to a large group of tertiary lymphoid organs that are found in cancer, autoimmune diseases, and atherosclerosis. Clinical correlation studies of the incidence of TLOs have shown beneficial associations in most cancers and infectious diseases but unfavorable outcomes in most autoimmune diseases, transplant rejection, and atherosclerosis. We aim to define the specific roles of ATLOs in cardiovascular diseases using a cross-tissue and cross-genotype approach using single cell RNA sequencing and spatial transcriptomics.

ATLO 属于一大类三级淋巴器官，存在于癌症、自身免疫性疾病和动脉粥样硬化中。关于 TLO 发病率的临床相关性研究表明，其与大多数癌症和传染病存在有益关联，但在大多数自身免疫性疾病、移植排斥和动脉粥样硬化中却会导致不良后果。我们旨在通过单细胞 RNA 测序和空间转录组学，采用跨组织和跨基因型的方法，明确 ATLO 在心血管疾病中的具体作用。

4 Neuroimmune cardiovascular interfaces (NICIs).神经免疫心血管接口 (NICI)。

As plaques lack innervation, the impact of neuronal control on atherosclerosis remains unknown. Because the peripheral nervous system uses the adventitia as their principle conduit to reach distant targets, we postulated that the peripheral nervous system may directly interact with diseased arteries. Surprisingly, wide-spread neuro-immune-cardiovascular interfaces (NICIs) arose in murine and human atherosclerosis: adventitia segments showed extensive axon networks which form an artery-brain-circuit.

由于斑块缺乏神经支配，神经元控制对动脉粥样硬化的影响尚不清楚。由于外周神经系统以血管外膜作为其到达远处目标的主要通道，我们推测外周神经系统可能与患病动脉直接相互作用。令人惊讶的是，在小鼠和人类动脉粥样硬化中出现了广泛的神经-免疫-心血管界面 (NICI)：外膜节段显示出广泛的轴突网络，形成了动脉-脑回路。

5 The choroid plexus is a major gateway for immune cells of the vascular system to enter the brain 脉络丛是血管系统免疫细胞进入大脑的主要通道

The choroid plexus is the principal gateway for blood-borne leukocytes to infiltrate the central nervous system in inflammatory and degenerative brain diseases. We identified a hitherto unrecognized choroid plexus pathology consisting of lipid and leukocytes. Demented Alzheimer Disease patients have higher lipid content in choroid plexus versus non-dementia cases.

脉络丛是血源性白细胞在炎症和退行性脑疾病中渗入中枢神经系统的主要通道。我们发现了一种迄今为止未被认识的脉络丛病理，由脂质和白细胞组成。痴呆型阿尔茨海默病患者的脉络丛脂质含量高于非痴呆型患者。

6 Neurovascular interfaces initiate the artery-brain-circuit (ABC) 神经血管界面启动动脉-脑回路 (ABC)

Murine NICIs established the ABCs to regulate cardiovascular functions. Abdominal-adventitia nociceptive afferents forms afferent artery-brain projection through spinal cord termed ABC sensor, which is linked to an efferent arm termed ABC effector forming a brain-artery projection. The brain integrates these peripheral signals and sends compensatory efferent effector signals from the hypothalamus and medulla to arteries.

小鼠 NICI 建立了 ABC 来调节心血管功能。腹壁外膜的痛觉传入神经经脊髓形成传入动脉-脑投射，称为ABC感受器，该感受器与传出臂相连，形成脑-动脉投射。脑整合这些外周信号，并将下丘脑和延髓的代偿性传出效应信号送至动脉。