Periodic Reporting for period 4 - Diet-namic (From fast food to healthy diet: Addressing the dynamic molecular mechanism of sequential diet switch-induced T cell plasticity for the purpose of developing new treatments for immuno-mediated diseases)
Période du rapport: 2021-06-01 au 2022-11-30
In short, we found that our immune system rapidly responds to changes in the diet, ranging from developing a status of immune depression or hyperactivation, to the extent of promoting cell death which licenses the efficacy of chemotherapy.
All in all, these results show the deep and rapid impact of the diet on our health. This project might provoke the idea that we can change the trajectory of many immune-related diseases, including cancer, by simply modulating what we do every day – eating. Finally, Diet-namic has provided a series of cellular and molecular mechanisms that can be targeted once simple dietary changes are no longer sufficient.
In parallel, we studied the molecular mechanisms of T cell adaptability and found one key signaling pathway, namely TGFβR/SMADs, which regulates this mechanism. In essence, we have made one initial step toward the development of future immune therapies that could “force” the anti-inflammatory fate of Th17 cells by targeting these specific molecular mechanisms, and thereby possibly reset the homeostasis in inflamed tissues of patients affected by Th17 cell-mediated immune-mediated inflammatory diseases.
Finally, we found that short-term consumption of a diet rich in tryptophan led to an increased concentration of the microbiota-derived metabolite indole-3-acetic acid (3-IAA) in the circulation of mice. The combination of 3-IAA and chemotherapy, licensed by neutrophil-derived myeloperoxidase, increases oxidative stress, reduces autophagic activity and ultimately halts colon and pancreatic cancer cell proliferation. Translating these findings back to humans, we found a strong correlation between the concentration of 3-IAA and the response to chemotherapy in two independent cohorts of pancreatic cancer patients.