Project Details
Projekt
Diet during pregnancy and maternal obesity: effects on the function of maternal TH17 and Treg cells and on subsequent offspring health
Subject Area
Pediatric and Adolescent Medicine
Immunology
Immunology
Term
from 2018 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 255154572
Unprecedented consumption of high sugar, fat and salt dietary components, commonly referred to as “Western” diet, is currently observed not only in developed countries, but also in developing countries and is considered one of the leading causes of obesity. It is apparent that a growing number of individuals are “forced” to consume this diet due to socioeconomic circumstances. In the year 2014, according to the World Health Organization, 600 million adults suffered from obesity. Many of them were also diagnosed with related metabolic or cardiovascular diseases. Interestingly, obesity is often associated with chronic and pathological activity of the immune system. Furthermore, epidemiological data indicate that consumption of Western diet during pregnancy and maternal obesity increase the risk of pregnancy complications, alter foetal development and account for poor children’s health later in life. This project aims to elucidate the cellular and molecular mechanisms underlying these effects. The main hypothesis is that Western diet and maternal obesity skew the maternal immune adaptation to pregnancy, especially the CD4 T cell response required to mount tolerance towards the semi-allogeneic foetus, towards inflammation. In turn, this inflammation leads to impaired foetal development and higher risk for the offspring to develop inflammatory diseases later in life. Considering that diet has a pivotal impact on the composition of the intestinal microbiota, which in turn is in continuous cross talk with the immune system, we will test if diet-mediated inflammation is mediated by the Western diet mediated imbalance of the maternal microbiota. Novel multi-cytokine fate reporter and conditional knock out mouse models will be used to test if maternal Western diet affects foetal development and offspring’s immunity via an altered function of distinct CD4 T cell subsets. To understand the molecular details of diet-induced changes in these mice, we will employ single cell transcriptomics, epigenetics, and state-of-the-art computational approaches. To translate the mechanistic insights from the mouse models into similarities and differences in humans, we will use data and biological samples from the prospective pregnancy cohort PRINCE. Our project will allow us to identify the causative link between Western diet and poor offspring immunity. This will help to identify new therapeutic targets such as pathogenic CD4 T cells, to develop new therapies, which aim to prevent the offspring having to suffer life-long health problems due to the social circumstances in which they are born.
DFG Programme
Clinical Research Units
