ECCO Grant Study Synopsis: Felix Grabherr

Felix Grabherr, ECCO Grant Awardee

Delineating an uptake-independent function of SR-BI in Paneth cells in metabolic gut inflammation

Felix Grabherr
© Felix Grabherr

Background & aim of research

Dietary lipids are associated with risk of developing Inflammatory Bowel Disease (IBD). Activity of glutathione peroxidase 4 (GPX4), an anti-oxidative selenoenzyme, is impaired in intestinal epithelial cells (IECs) from patients with ileal Crohn’s Disease (CD). GPX4 controls intestinal inflammation triggered by dietary polyunsaturated fatty acids (PUFAs) and dietary PUFA uptake is associated with CD flares. SR-BI (encoded by Scarb1) is a membrane-bound receptor, mainly reported to be involved in the uptake of cholesterol, and cholesterol uptake has been described to play a role in ferroptosis induction, a cell death pathway which is regulated by GPX4. Paneth cells (PCs), specialised IECs within the small intestine, have been described to be the origin of intestinal inflammation. Preliminary data indicate that PCs sense and translate dietary PUFA stress into intestinal inflammation. 

Methodology/experiments that will be used

We are working with genetically modified cells lacking SR-B1 or GPX4 and mice lacking both proteins specifically in PCs to decipher how SR-B1 regulates metabolism-induced intestinal inflammation.

Anticipated main impact

In this study, we are seeking to cast light on a role for SR-BI in PCs in metabolism-induced intestinal inflammation, which could help to explain how dietary PUFAs trigger intestinal inflammation emanating from PCs and could provide a clue to the small intestinal nature of experimental gut inflammation.

Proposed timeline

Currently we are focused on understanding the mechanistic impact of SR-B1 on metabolic inflammation in the gut; as the experiments (especially the in vivo setup) are time-intense, we aim to complete the project in the middle of 2024.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports