Mechanistic Insights into T-2 Toxin-Induced Thymic Epithelial Cell Injury and Immunotoxicity via the ROS-NF-κB-NLRP3 Signaling Axis

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Abstract
Thymic epithelial cells (TECs) are critical for thymic structure and function, yet the impact of T-2 toxin (T-2) on TECs and related molecular pathways remains unclear. This study sheds light on the mechanisms of T-2-induced TEC damage, focusing on the ROS-NF-κB-NLRP3 signaling axis. The in vivo and in vitro analyses suggest that T-2 induces TEC injury through ROS-driven NLRP3 inflammasome activation, NF-κB signaling, inflammation, and apoptosis. Molecular docking analysis verified the binding of T-2 to critical components involved in oxidative stress, inflammatory signaling pathways, and apoptosis. These findings were further supported by therapeutic interventions targeting ROS and NLRP3. N-acetylcysteine (NAC) effectively reduced ROS levels, suppressed NF-κB signaling, inhibited NLRP3 activation, and mitigated inflammation and apoptosis, effects mirrored by the NLRP3 inhibitor MCC950, emphasizing the critical role of ROS-mediated NLRP3 inflammasome activation through NF-κB signaling in T-2-induced TEC damage. Concurrently, inhibition of the NF-κB signaling further suppressed ROS levels, NLRP3 inflammasome activation, and apoptosis in MTEC1 cells, emphasizing the pivotal function of the ROS-NF-κB-NLRP3 axis in the pathogenesis of T-2-induced thymic injury. Our study offers an in-depth insight into the mechanisms driving T-2-induced immunotoxicity and identifies potential therapeutic strategies targeting these pathways to mitigate thymic injury and preserve immune function.
Funding Information
  • National Natural Science Foundation of China (32102632)
  • Xinjiang University (1366020120)
  • Earmarked Fund for China Agriculture Research System (2024CYJSTX12-10)
  • Henan Provincial Science and Technology Research Project (242102321133)
  • Henan Province Higher Education Young Backbone Teacher Training Program (2024GGJS141)
  • Postgraduate Education Reform and Quality Improvement Project of Henan Province (YJS2024JD51)

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