• Shock · Aug 2024

    D4-Chip Reveals Impaired T Cell Function in Sepsis: Insights from Plasma Microenvironment Analysis and Mitochondrial Targeted Therapy.

    • Lijuan Liu, Ruoyu Wang, Xuexue Pu, Yutao Zha, Xiao Yang, Xiao Fang, Yong Liu, Min Shao, Ling Zhu, Xiaoou Ren, Guoqing Deng, and Ke Yang.
    • The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
    • Shock. 2024 Aug 12.

    BackgroundSepsis, a systemic inflammation syndrome initiated by infection, poses significant challenges due to its intricate pathophysiology. T cells play a crucial role in combating infections during sepsis. Despite previous observations indicating T cell dysfunction in sepsis, reliable in-vitro detection methods were lacking, and the factors influencing these impairments remained unclear.MethodsWe developed a novel method using the D4-Chip to assess sepsis T cell migration function. This microfluidic platform enabled precise analysis of migration function under controlled conditions. Additionally, We explored the impact of the plasma microenvironment on T cell behavior, along with the redox environment in sepsis, and assessed the potential efficacy of Mitoquinone mesylate (MitoQ), a mitochondrial-targeted drug.ResultsOur findings revealed impaired migration function in sepsis T cells compared to healthy controls. Interestingly, sepsis plasma enhanced the migration of healthy T cells, yet incubation with healthy plasma did not fully restore migration impairments in sepsis T cells. Subsequent investigations uncovered a significant increase in NADH/NAD+ levels in sepsis T cells, with healthy T cells exposed to various sepsis plasma conditions also showing elevated NADH/NAD+ levels. Importantly, MitoQ normalized abnormal intracellular NADH/NAD+ levels and enhanced the migration ability of T cells.ConclusionsShort-term incubation with sepsis plasma does not directly inhibit T cell migration but instead affects T cell function by disrupting the intracellular redox environment. Improving the intracellular redox environment of sepsis patients contributes to restoring impaired migration and proliferation, with MitoQ demonstrating therapeutic potential.Copyright © 2024 by the Shock Society.

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