We study development and function of the innate immune system, in particular of innate lymphoid cells (ILC). A current focus is to obtain a molecular understanding of how the innate immune system, by integrating environmental signals (such as those derived from nutrients, microbiota, circadian rhythm) contributes to tissue physiology. Recent studies have revealed ever more intriguing relationships between innate immune system components and basic developmental and biological processes that are likely to reveal unsuspected pathways by which the immune system might be plumbed to improve health and healthspan. These lines of research have suggested new functions of the immune system for processes such as tissue homeostasis, morphogenesis, metabolism, regeneration and growth. Our research is developing by crossing boundaries of disciplines (immunology, microbiology, developmental biology, stem cell biology, nutrition sciences, molecular medicine etc.) and is, by nature, highly interdisciplinary.
Innate lymphoid cells (ILC) are tissue-resident innate lymphocytes that are involved in immunity to infections but are also deeply integrated in the regulation of tissue function. For example, our recent work revealed that ILC support nutrient uptake in the small intestine and that changes in ILC effector programs affect systemic metabolism (Gronke, Nature 2019; Guendel, Immunity 2020; Diefenbach, Immunity 2020). In this project, we are exploring the role of ILC3 and ILC3-derived effector molecules for metabolic adaptation during pregnancy. Pregnancy is one of the biggest challenges to metabolic demands in life and it constitutes a physiological state of metabolic syndrome. The role of immune system components in general and of ILC in adapting the organism to this demand is unknown. Our preliminary data indicate that pregnancy is linked to intestinal growth resulting in a larger number of enterocytes for nutrient absorption. Interestingly, mice lacking ILC3 had impaired growth of the intestinal organ and nutrient absorption was reduced resulting in lower birth weight of the offspring and reduced caloric content of breast milk. The project will address the following specific aims:
Specific Aim 1: To explore how ILC3 mechanistically regulate epithelial growth during pregnancy and lactation;
Specific Aim 2: To interrogate the epithelial cell programs that are controlled by ILC3;
Specific Aim 3: To determine how these changes affect systemic metabolism and health of the offspring.