Details

Autor(en) / Beteiligte

• Becker, Björn
• Wottawa, Felix
• Bakr, Mohamed
• Koncina, Eric
• Mayr, Lisa
• Kugler, Julia
• Yang, Guang
• Windross, Samuel J.
• Neises, Laura
• Mishra, Neha
• Harris, Danielle
• Tran, Florian
• Welz, Lina
• Schwärzler, Julian
• Bánki, Zoltán
• Stengel, Stephanie T.
• Ito, Go
• Krötz, Christina
• Coleman, Olivia I.
• Jaeger, Christian
• Haller, Dirk
• Paludan, Søren R.
• Blumberg, Richard
• Kaser, Arthur
• Cicin-Sain, Luka
• Schreiber, Stefan
• Adolph, Timon E.
• Letellier, Elisabeth
• Rosenstiel, Philip
• Meiser, Johannes
• Aden, Konrad

Titel

Serine metabolism is crucial for cGAS-STING signaling and viral defense control in the gut

Ist Teil von

• iScience, 2024-03, Vol.27 (3), p.109173-109173, Article 109173

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •ER stress reprograms serine and 1C metabolism to promote GSH supply in IECs•ER stress abrogates cGAS/STING signaling via the accumulation of ROS•Antioxidant therapy restores virus defense control in ER-stressed IECs•ER stress-mediated rewiring of serine metabolism is a key molecular feature in IBD Virology; Microbial metabolism