Immune Response and Inflammation
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It is reported that temperatures associated with moderate-grade fevers both enhance the metabolism, proliferation, and effector function of mouse CD4 T cells and dampen regulatory T cell suppressive potential.
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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 (TH1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways. Although many TH1 cells subjected to such temperatures died, surviving TH1 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 TH1 cells. TH1 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 TH1 cells to maintain genomic integrity and enhance effector functions.
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@article{Chowdhury2024Subset,
title = {Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation},
author = {Nowrin U. Chowdhury and Darren R. Heintzman and Rachael C. Sinard and Emilie L. Fisher and Xiang Ye and Andrew R. Patterson and Joel H. Elasy and Kelsey Voss and Channing Chi and Ayaka Sugiura and Gabriel J Rodriguez-Garcia and Emily N. Arner and Evan S. Krystoviak and Frank M. Mason and Yasmine T. Toudji and KayLee K. Steiner and Wasay Khan and Lana M. Olson and Angela Jones and Hanna S. Hong and Lindsay E Bass and Katherine L. Beier and Wentao Deng and Costas A. Lyssiotis and Dawn C. Newcomb and Alexander G. Bick and W. Kimryn Rathmell and John T. Wilson and Jeffrey C. Rathmell},
journal = {Science Immunology},
year = {2024},
doi = {10.1126/sciimmunol.adp3475},
url = {https://doi.org/10.1126/sciimmunol.adp3475}
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