Maloney Elizabeth, Duffy Darragh
Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France.
Frontiers of Innovation in Research and Education PhD Program, LPI Doctoral School, Paris, France.
Discov Immunol. 2024 Jan 30;3(1):kyae001. doi: 10.1093/discim/kyae001. eCollection 2024.
Fever is a hallmark symptom of disease across the animal kingdom. Yet, despite the evidence linking temperature fluctuation and immune response, much remains to be discovered about the molecular mechanisms governing these interactions. In patients with rheumatoid arthritis, for instance, it is clinically accepted that joint temperature can predict disease progression. But it was only recently demonstrated that the mitochondria of stimulated T cells can rise to an extreme 50°C, potentially indicating a cellular source of these localized 'fevers'. A challenge to dissecting these mechanisms is a bidirectional interplay between temperature and immunity. Heat shock response is found in virtually all organisms, activating protective pathways when cells are exposed to elevated temperatures. However, the temperature threshold that activates these pathways can vary within the same organism, with human immune cells, in particular, demonstrating differential sensitivity to heat. Such inter-cellular variation may be clinically relevant given the small but significant temperature differences seen between tissues, ages, and sexes. Greater understanding of how such small temperature perturbations mediate immune responses may provide new explanations for persistent questions in disease such as sex disparity in disease prevalence. Notably, the prevalence and severity of many maladies are rising with climate change, suggesting temperature fluctuations can interact with disease on multiple levels. As global temperatures are rising, and our body temperatures are falling, questions regarding temperature-immune interactions are increasingly critical. Here, we review this aspect of environmental interplay to better understand temperature's role in immune variation and subsequent risk of disease.
发热是整个动物界疾病的一个标志性症状。然而，尽管有证据表明体温波动与免疫反应有关，但关于控制这些相互作用的分子机制仍有许多有待发现。例如，在类风湿性关节炎患者中，临床上公认关节温度可以预测疾病进展。但直到最近才证明，受刺激的T细胞的线粒体温度可以升至极端的50°C，这可能表明这些局部“发热”存在细胞来源。剖析这些机制的一个挑战是温度与免疫之间的双向相互作用。热休克反应几乎在所有生物体中都存在，当细胞暴露于高温时会激活保护途径。然而，激活这些途径的温度阈值在同一生物体内可能会有所不同，特别是人类免疫细胞对热表现出不同的敏感性。考虑到不同组织、年龄和性别之间存在微小但显著的温度差异，这种细胞间的差异可能具有临床相关性。更深入地了解这种微小的温度扰动如何介导免疫反应，可能会为疾病中一些长期存在的问题提供新的解释，比如疾病患病率中的性别差异。值得注意的是，随着气候变化，许多疾病的患病率和严重程度都在上升，这表明温度波动可以在多个层面与疾病相互作用。随着全球气温上升，而我们的体温却在下降，关于温度与免疫相互作用的问题变得越来越关键。在这里，我们回顾环境相互作用的这一方面，以更好地理解温度在免疫变异和随后的疾病风险中的作用。
