The influence of lymph node-specific stromal cells on the funktion of gut draining lymph nodes during a high fat diet

高脂肪饮食期间淋巴结特异性基质细胞对肠道引流淋巴结功能的影响

• 批准号: 253114153
• 负责人: Dr. Manuela Büttner, since 4/2014
• 金额: --
• 依托单位: Institut für Funktionelle und Angewandte Anatomie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/253114153?language=en
• 关键词: influence; lymph; node; specific; stromal

In recent years it was shown that stromal cells of peripheral (pLN) and mesenteric (mLN) lymph nodes have the competence to influence immune response reactions or tolerance induction. We established a transplantation model in which we resected the mLN of the host and inserted a pLN of a recipient. The pLN regenerated resulting in normal structures and functionality. This work was done during the period of the SFB -pathobiology of the gut mucosa-. It was documented in several papers that only stromal cells remained in the tissue while the immune cells were exchanged for host cells. Thus, stromal cells have an impact on immune responses in the gut and on oral tolerance induction. However, the expression pattern seems to be fixed after birth, because after transplantation of pLN into the mesentery homing molecules did not adapt to the specific region. Isolation of stromal cell subsets and investigation of their transcriptional profiles revealed that pLN and mLN had different transcriptional profiles resulting in optimal conditions to induce region-specific immune responses and tolerance induction. An interesting result was that only mLN stromal cells express lipid converting enzymes. Lipids taken up and modulated by the gut mucosa were adjusted to the afferent lymphatics. After that they were released into the blood circulation for further use in different organs such as the liver. However, it was completely neglected that the lymph has to pass the mLN. Therefore, until now it remains unclear, whether the function of the mLN is influenced by the incoming lipids or whether the mLN itself has a metabolic function.A high fat diet results in an increase of mesenteric and peripheral fat tissue. This is often accompanied by diseases such as diabetes type I, cardiovascular disorders and inflammatory bowel diseases. It is not known whether the function of mLN is influenced by high fat diets. Therefore, the current project deals with the question, on the one hand, whether the mLN and especially the stromal cells are influenced by passing lipids, and on the other hand, we want to ask whether stromal cells and/or immune cells are involved in the metabolism of lipids. We also will address the question, whether stromal cells express lipid-converting enzymes.

近年来研究表明，外周淋巴结（pLN）和肠系膜淋巴结（mLN）的基质细胞具有影响免疫应答反应或耐受诱导的能力。我们建立了一个移植模型，在这个模型中，我们切除了宿主的mLN，并植入了受体的pLN。pLN再生，导致正常的结构和功能。这项工作是在SFB -肠道粘膜病理生物学-期间完成的。在几篇论文中记录了只有基质细胞保留在组织中，而免疫细胞被宿主细胞交换。因此，基质细胞对肠道中的免疫应答和口服耐受诱导具有影响。然而，表达模式似乎是固定的出生后，因为移植后的pLN到肠系膜归巢分子没有适应的特定区域。基质细胞亚群的分离和它们的转录谱的调查显示，pLN和mLN具有不同的转录谱，导致诱导区域特异性免疫应答和耐受诱导的最佳条件。一个有趣的结果是，只有mLN基质细胞表达脂质转化酶。由肠粘膜吸收和调节的脂质根据传入神经调节。之后，它们被释放到血液循环中，以进一步用于不同的器官，如肝脏。然而，完全忽略了淋巴必须通过mLN。因此，到目前为止，尚不清楚mLN的功能是否受到脂质的影响，或者mLN本身是否具有代谢功能。高脂饮食导致肠系膜和外周脂肪组织增加。这往往伴随着疾病，如糖尿病I型，心血管疾病和炎症性肠病。尚不清楚mLN的功能是否受到高脂饮食的影响。因此，目前的项目涉及的问题，一方面，mLN，特别是基质细胞是否受到通过脂质的影响，另一方面，我们想问基质细胞和/或免疫细胞是否参与脂质的代谢。我们也将解决这个问题，是否基质细胞表达脂质转化酶。