| Autor: |
Björn Becker, Felix Wottawa, Mohamed Bakr, Eric Koncina, Lisa Mayr, Julia Kugler, Guang Yang, Samuel J. Windross, Laura Neises, Neha Mishra, Danielle Harris, Florian Tran, Lina Welz, Julian Schwärzler, Zoltán Bánki, Stephanie T. Stengel, Go Ito, Christina Krötz, Olivia I. Coleman, Christian Jaeger, Dirk Haller, Søren R. Paludan, Richard Blumberg, Arthur Kaser, Luka Cicin-Sain, Stefan Schreiber, Timon E. Adolph, Elisabeth Letellier, Philip Rosenstiel, Johannes Meiser, Konrad Aden |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 27, Iss 3, Pp 109173- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2024.109173 |
| Popis: |
Summary: Inflammatory bowel diseases are characterized by the chronic relapsing inflammation of the gastrointestinal tract. While the molecular causality between endoplasmic reticulum (ER) stress and intestinal inflammation is widely accepted, the metabolic consequences of chronic ER stress on the pathophysiology of IBD remain unclear. By using in vitro, in vivo models, and patient datasets, we identified a distinct polarization of the mitochondrial one-carbon metabolism and a fine-tuning of the amino acid uptake in intestinal epithelial cells tailored to support GSH and NADPH metabolism upon ER stress. This metabolic phenotype strongly correlates with IBD severity and therapy response. Mechanistically, we uncover that both chronic ER stress and serine limitation disrupt cGAS-STING signaling, impairing the epithelial response against viral and bacterial infection and fueling experimental enteritis. Consequently, the antioxidant treatment restores STING function and virus control. Collectively, our data highlight the importance of serine metabolism to allow proper cGAS-STING signaling and innate immune responses upon gut inflammation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
