Project Details
Projekt
Potentiating ferroptosis as treatment of allergic airway inflammation
Applicant
Professor Christoph Wilhelm, Ph.D.
Subject Area
Cell Biology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 461705360
Innate lymphoid cells (ILC) serve the major task of protection and maintenance of the tissue barrier. However, chronic activation of ILC can promote inflammation and contribute to inflammatory disorders affecting barrier sites. Investigating the metabolic pathways controlling the function of pathogenic group type 2 innate lymphoid cells (ILC2) in airway inflammation we discovered that the acquisition of external lipids for proliferation is a prerequisite for chronic activation. However, increased lipid uptake also increases the exposure of cells to lipid radicals, which can cause the non-aopototic cell death ferroptosis. To balance increased exposure to lipid peroxidation ILC2 upregulate the expression of cellular antioxidant systems upon activation. Hence we hypothesize that increased lipid metabolism driving pathogenic ILC2 responses requires the simultaneous counterbalance of lipid peroxidation to prevent ferroptosis. As a consequence, targeting this protective mechanism may induce ferroptosis and preclude the induction of pathogenic ILC2 and thus the development of chronic airway inflammation. To investigate our hypothesis we will assess the function of pro- and anti- ferroptoic pathways in ILC2 biology and ILC2-mediated airway inflammation. Overall, targeting ferroptosis as a mechanism promoting pathogenic ILC2 responses offers a previously unexplored approach to treat chronic inflammation. Thus with our research we aim to the tackle one major societal challenge, the dramatic increase in chronic inflammatory disorders in the Western World and to identify novel targets for therapeutic intervention.
DFG Programme
Priority Programmes
