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 (T H 1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways. Although many T H 1 cells subjected to such temperatures died, surviving T H 1 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 T H 1 cells. T H 1 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 T H 1 cells to maintain genomic integrity and enhance effector functions.

中文翻译：

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亚群特异性线粒体应激和 DNA 损伤塑造 T 细胞对发热和炎症的反应


热量是炎症的一个主要特征，但它对免疫细胞的影响仍然不确定。我们表明，中度发热温度 （39°C） 增加了小鼠 CD4 T 细胞的代谢、增殖和炎症效应器活性，同时降低了调节性 T 细胞抑制能力。然而，热暴露的辅助性 T 细胞 1 （T H 1） 选择性地产生线粒体应激和 DNA 损伤，从而激活 Trp53 和干扰素基因通路的刺激剂。尽管许多 T H 1 细胞在这种温度下死亡，但存活的 T H 1 细胞表现出线粒体质量增加和活性增强。电子传递链复合物 1 （ETC1） 在发热范围内迅速受损，这种现象对 T H 1 细胞特别有害。在人类慢性炎症中也检测到 DNA 损伤和 ETC1 特征升高的 T H 1 细胞。因此，与发热相关的温度会破坏 ETC1 选择性地驱动 T H 1 细胞的凋亡或适应，以维持基因组完整性并增强效应器功能。