biostudies-literatureHeintzman DRNEI NIH HHSNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHSNCI NIH HHSNIAMS NIH HHSeadp3475https://www.ebi.ac.uk/biostudies/studies/S-EPMC11607909biostudies-literatureUnknown9(99)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_H1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways. Although many T_H1 cells subjected to such temperatures died, surviving T_H1 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_H1 Science immunologySubset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation.PMC11607909R01 AI153167P30 DK058404R01 HL136664R01 HL118979R01 CA217987P30 EY008126R01 DK105550T32 DK101003T32 AI112541P30 DK020593P30 CA068485K00 CA253718U2C DK059637T32 AR059039R01 CA245134U01 AI176244Khan WChi CBass LToudji YTMason FMRathmell JCYe XNewcomb DCWilson JTElasy JHBeier KLDeng WHeintzman DRRodriguez-Garcia GJPatterson ARHong HSSinard RCSteiner KKOlson LMRathmell WKChowdhury NUSugiura AArner ENVoss KJones ALKrystoviak ESFisher ELBick AGLyssiotis CAfalseSubset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation.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_H1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways. Although many T_H1 cells subjected to such temperatures died, surviving T_H1 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_H1 2024-01-01T00:00:00Z2024 Sep2026-06-03T11:33:24.09Z2026-04-27T03:10:34.533ZS-EPMC116079093930301810.1126/sciimmunol.adp3475