Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Sci Immunol. 2024 Sep 20;9(99):eadp3475. doi: 10.1126/sciimmunol.adp3475.
Heat is a cardinal feature of inflammation, yet its impacts on immune cells remain uncertain. We show that moderate-grade fever temperatures (39°C) increased murine CD4 T cell metabolism, proliferation, and inflammatory effector activity while decreasing regulatory T cell suppressive capacity. However, heat-exposed T helper 1 (T1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways. Although many T1 cells subjected to such temperatures died, surviving T1 cells exhibited increased mitochondrial mass and enhanced activity. Electron transport chain complex 1 (ETC1) was rapidly impaired under fever-range temperatures, a phenomenon that was specifically detrimental to T1 cells. T1 cells with elevated DNA damage and ETC1 signatures were also detected in human chronic inflammation. Thus, fever-relevant temperatures disrupt ETC1 to selectively drive apoptosis or adaptation of T1 cells to maintain genomic integrity and enhance effector functions.
发热是炎症的一个主要特征，但它对免疫细胞的影响仍不确定。我们发现，中等程度的发热（39°C）会增加小鼠 CD4 T 细胞的代谢、增殖和炎症效应器活性，同时降低调节性 T 细胞的抑制能力。然而，暴露于热中的辅助性 T 细胞 1（T1）细胞选择性地发展线粒体应激和 DNA 损伤，激活 Trp53 和干扰素基因刺激物途径。尽管许多 T1 细胞在这样的温度下死亡，但存活下来的 T1 细胞表现出增加的线粒体质量和增强的活性。电子传递链复合物 1（ETC1）在发热范围内的温度下迅速受损，这种现象对 T1 细胞特别有害。在人类慢性炎症中也检测到具有升高的 DNA 损伤和 ETC1 特征的 T1 细胞。因此，与发热相关的温度会破坏 ETC1，从而选择性地驱动 T1 细胞凋亡或适应，以维持基因组完整性并增强效应功能。
