Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism.
Kota KokuboKiyoshi HiraharaMasahiro KiuchiKaori TsujiYuki ShimadaYuri SonobeRie ShinmiTakahisa HishiyaChiaki IwamuraAtsushi OnoderaToshinori NakayamaPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
CD4 + memory T cells are central to long-lasting protective immunity and are involved in shaping the pathophysiology of chronic inflammation. While metabolic reprogramming is critical for the generation of memory T cells, the mechanisms controlling the redox metabolism in memory T cell formation remain unclear. We found that reactive oxygen species (ROS) metabolism changed dramatically in T helper-2 (Th2) cells during the contraction phase in the process of memory T cell formation. Thioredoxin-interacting protein (Txnip), a regulator of oxidoreductase, regulated apoptosis by scavenging ROS via the nuclear factor erythroid 2-related factor 2 (Nrf2)-biliverdin reductase B (Blvrb) pathway. Txnip regulated the pathology of chronic airway inflammation in the lung by controlling the generation of allergen-specific pathogenic memory Th2 cells in vivo. Thus, the Txnip-Nrf2-Blvrb axis directs ROS metabolic reprogramming in Th2 cells and is a potential therapeutic target for intractable chronic inflammatory diseases.
Keyphrases
- cell cycle arrest
- induced apoptosis
- oxidative stress
- reactive oxygen species
- cell death
- working memory
- nuclear factor
- endoplasmic reticulum stress
- dna damage
- transcription factor
- nlrp inflammasome
- signaling pathway
- toll like receptor
- pi k akt
- cell proliferation
- amino acid
- binding protein
- smooth muscle
- allergic rhinitis