CHOLCONTROL

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 508(7494):123-7), postnatal small intestinal lymphoid tissue development (Kiss, Science 2011 334(6062):1561-5) and in gut immunity (Gronke, Nature 2019 566(7743):249-253). Its ontogeny and maintenance rely on the transcription factor Retinoic acid orphan receptor – gamma-t (RORyt). We have shown that RORyt 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 (RORyt) expression (van de Pavert, Nature 2014 508(7494):123-7). However, next to induction of Rorc expression, the activity of RORyt was shown to be modulated by cholesterol metabolism intermediates (Santori, Cell Metab 2015 21(2):286-298). Therefore, in this study we aim to establish the effect of maternal dietary cholesterol on RORyt 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.