Wilhelm Group

A major societal challenge in the Western world is the dramatic increase in chronic inflammatory disorders manifesting at barrier sites, including allergies, asthma (lung), psoriasis (skin), and inflammatory bowel disease (IBD; intestine). Recent advances identified a new group of innate immune cells primarily residing at such barrier surfaces, which were named innate lymphoid cells (ILC). Three distinct ILC subsets have been described to reside in the gut, lung and skin. Type 1 ILC (ILC1) express the transcription factor T-bet, produce the cytokine interferon (IFN)-γand are implicated in protecting against intracellular pathogens such as Toxoplasma gondii ILC2 express the transcription factor GATA-3 and produce the cytokines IL-5, IL-9, IL-13 and amphiregulin. ILC3 are characterized by the expression of the transcription factor Rorgt and the cytokine IL-22. Thus, the major task of ILC is the protection and maintenance of the tissue barrier. However, chronic activation of ILC can promote inflammation and contribute to inflammatory disorders manifesting at barrier sites. In general, the etiology of barrier diseases is poorly understood but changes in life-style coinciding with westernization, such as abundant nutritional uptake and increased hygiene, leading to an overall absence of parasitic infections are suggested to play a role in disease development.

A major current goal of our research is to understand the difference between protective and pathogenic ILC function by studying the metabolic regulation of ILC in health and disease. In particular we work under the assumption that the metabolic adaptation of ILC, which allows their survival in nutrient deprived environments (e.g. starvation, vitamin A deficiency) is an important evolutionary restraint lost in Industrialized countries. Our recent data suggests that protective ILC2 mediated anti-helminth immune responses are dependent on fatty acid metabolism but not glycolysis and that vitamin A deficiency increases fatty acid oxidation in ILC2. Basing the function of ILC2 elicited in the context of helminth infection on fatty acid metabolism may have been important to mediate tissue repair and worm expulsion in settings of malnutrition and low glucose. However, this scenario dictated by chronic helminth infections and low nutrient availability has dramatically changed in the western world and it is completely unknown whether both protective and pathogenic ILC responses underlie a similar metabolic control. Currently, we are attempting to identify metabolic pathways driving disease pathology in order to identify novel pharmacological inhibitors that could be used to treat disease. In addition, by mimicking situations of nutrient deprivation we are currently testing different dietary intervention strategies with the aim to identify novel therapeutic treatments to target ILC-mediated pathologies. 

Thus, with our research we aim to contribute to the understanding of one major societal challenge, the dramatic increase in chronic inflammatory disorders and to identify novel potential targets for therapeutics as well as the possibility of dietary interventions strategies for their treatment.