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

• Applicant: Dr. Manuela Büttner, since 4/2014
• Subject Area: Gastroenterology
• Term: from 2014 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 253114153

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.

• DFG Programme: Research Grants
• Participating Persons: Professorin Dr. Christine Falk; Professor Dr. Reinhold Förster; Dr. Jan Hegermann
• Ehemalige Antragstellerin: Privatdozentin Dr. Ulrike Bode, until 4/2014 (†)