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.

近年来的研究表明，外周(PLN)和肠系膜(MLN)淋巴结的间质细胞具有影响免疫反应或诱导耐受的能力。我们建立了一种移植模型，在该模型中，我们切除了宿主的MLN并植入了受体的PLN。PLN再生，结构和功能正常。这项工作是在SFB期间完成的-肠道粘膜的病理生物学-。几篇论文证明，当免疫细胞与宿主细胞交换时，只有基质细胞留在组织中。因此，基质细胞对肠道内的免疫反应和口服耐受诱导有影响。然而，这种表达模式在出生后似乎是固定的，因为PLN移植到肠系膜归巢分子后并不适应特定的区域。基质细胞亚群的分离和转录谱研究表明，PLN和MLN具有不同的转录谱，从而获得了诱导区域特异性免疫反应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换酶。被肠粘膜摄取和调节的脂类被调节到传入淋巴管。之后，它们被释放到血液循环中，进一步用于不同的器官，如肝脏。然而，淋巴必须通过MLN这一点被完全忽视了。因此，到目前为止还不清楚MLN的功能是否受到进入的脂质的影响，或者MLN本身是否具有代谢功能。高脂饮食会导致肠系膜和周围脂肪组织的增加。这通常伴随着诸如I型糖尿病、心血管疾病和炎症性肠道疾病等疾病。目前尚不清楚MLN的功能是否受到高脂肪饮食的影响。因此，本课题一方面探讨间质细胞，尤其是间质细胞是否受到过氧化脂质的影响，另一方面，探讨间质细胞和/或免疫细胞是否参与脂质代谢。我们还将解决基质细胞是否表达脂类转换酶的问题。