Transgenerational impact of maternal diets by regulating RORγt activity in embryonic and postnatal ILC3

• Applicant: Professor Dr. Andreas Diefenbach
• Subject Area: Immunology ; Gastroenterology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545535253

Innate Lymphoid Cells (ILCs) have been implicated in tissue remodeling and immune regulation. The type 3 family of the ILCs (ILC3) are involved in embryonic lymph node development (van de Pavert, Nature 2014), postnatal small intestinal lymphoid tissue development (Kiss, Science 2011) and in gut immunity (Gronke, Nature 2019). Its ontogeny and maintenance rely on the transcription factor Retinoic Acid Orphan Receptor gamma-t (RORγt). We have shown that RORγt can be induced by retinoic acid, a metabolic product of Vitamin A. Moreover, Vitamin A levels within the maternal diet regulated ILC3 differentiation within the embryo by regulating Rorc (encoding RORγt) expression (van de Pavert, Nature 2014). However, next to induction of Rorc expression, the activity of RORγt was shown to be modulated by cholesterol metabolism intermediates (Santori, Cell Metab 2015). Therefore, in this study, we aim to establish the effect of maternal dietary cholesterol on RORγt activity and on ILC3 differentiation. Moreover, we will establish whether maternal dietary cholesterol imprints immunity in the adult offspring using the complementary and synergistic approaches of our laboratories.

• DFG Programme: Research Grants
• International Connection: France
• Partner Organisation: Agence Nationale de la Recherche / The French National Research Agency
• Cooperation Partner: Serge van de Pavert, Ph.D.