Project B09
Tissue-derived eicosanoids as modulators of Treg cell induction, stability and function
Background
Distinct tissue-derived signals drive regulatory T cell induction and shape their heterogeneity, functionality and stability in chronic type-2 inflammation, e.g. in allergic asthma. We have recently identified arachidonic acid-derived eicosanoid lipid mediators (LMs) as local, tissue-derived metabolites that mediate the suppression of Th2-driven allergic airway inflammation (AAI).
We hypothesize that the tissue-specific eicosanoid pool regulates transcription factors and signaling pathways that control Treg cell development.
Strategy
We aim to decipher how distinct tissue derived eicosanoids act as pro- or anti-inflammatory mediators during onset and control of AAI. For this, we characterize in detail lung-derived eicosanoids with pro- or anti-inflammatory effects on AAI to modulate Treg cell development and investigate underlying mechanisms by selective inhibition and CRISPR-editing of eicosanoid-receptor pathways. We use pharmacological, sequencing and metabolomics approaches as well as genetic mouse lines with conditional deficiencies to interrogate the PGE2-Treg cell axis during AAI and lastly, we will investigate via tissue-region profiling the Treg-myeloid cell crosstalk during AAI.