ArticleProceedings of the National Academy of Sciences of the United States of America2020
Febrile temperature change modulates CD4 T cell differentiation via a TRPV channel-regulated Notch-dependent pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 60 citations in OpenAlex.
- Nutrigenomic Potentials of Phytobiotics Against Heat Stress and Allied Afflictions in Livestock Species-An In Silico Supported Review.Food science & nutrition · 2026Review
- Immunometabolic and immune regulatory functions of capsaicin in cancer: mechanistic insights and emerging perspectives.Frontiers in immunology · 2026Review
- Fever Inspiration: Precision Engineering for Safe and Systemic Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- T cell-specific HIF-2α attenuates colitis by antagonizing notch-driven Th2 differentiations.Frontiers in immunology · 2026Article
- Association of fever and infections with the subsequent risk of atopic diseases in children with genetic susceptibility for T1D: Results from the TEDDY cohort study.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2025Article
- Febrile temperature-regulated TRPV1 in CD4Journal of neuroinflammation · 2025Article
- Mitochondrial response to fever boosts TImmunometabolism (Cobham, Surrey) · 2025Article
- Effects of Climate Change on the Immune System: A Narrative Review.Health science reports · 2025Article
- Metabolic and stress response adaptations in T cells to fever and physiological heat.Trends in immunology · 2025Review
- What's cooking? The effect of temperature on the immune response.Frontiers in immunology · 2025Review
- Cold-blooded vertebrate utilizes behavioral fever to alleviate T cell apoptosis and optimize antimicrobial immunity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Identification of ANXA1 as a Novel Upstream Negative Regulator of Notch1 Function in AML.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation.Science immunology · 2024Article
- The immunology of sickness metabolism.Cellular & molecular immunology · 2024Review
- ThermoPCD: a database of molecular dynamics trajectories of antibody-antigen complexes at physiologic and fever-range temperatures.Database : the journal of biological databases and curation · 2024Article
- Temperature impacts the bovine ex vivo immune response towards Mycoplasmopsis bovis.Veterinary research · 2024Article
- Temperature control in sepsis.Frontiers in medicine · 2023Review
- Therapeutic hyperthermia for the treatment of infection-a narrative review.Frontiers in physiology · 2023Review
- Amplifying cancer treatment: advances in tumor immunotherapy and nanoparticle-based hyperthermia.Frontiers in immunology · 2023Review
- The role of the Notch signalling pathway in the pathogenesis of ulcerative colitis: from the perspective of intestinal mucosal barrier.Frontiers in medicine · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fever is a conserved and prominent response to infection. Yet, the issue of how CD4 T cell responses are modulated if they occur at fever temperatures remains poorly addressed. We have examined the priming of naive CD4 T cells in vitro at fever temperatures, and we report notable fever-mediated modulation of their cytokine commitment. When naive CD4 T cells were primed by plate-bound anti-CD3 and anti-CD28 monoclonal antibodies at moderate fever temperature (39 °C), they enhanced commitment to IL4/5/13 (Th2) and away from IFNg (Th1). This was accompanied by up-regulation of the Th2-relevant transcription factor GATA3 and reduction in the Th1-relevant transcription factor Tbet. Fever sensing by CD4 T cells involved transient receptor potential vanilloid cation channels (TRPVs) since TRPV1/TRPV4 antagonism blocked the febrile Th2 switch, while TRPV1 agonists mediated a Th2 switch at 37 °C. The febrile Th2 switch was IL4 independent, but a γ-secretase inhibitor abrogated it, and it was not found in Notch1-null CD4 T cells, identifying the Notch pathway as a major mediator. However, when naive CD4 T cells were primed via antigen and dendritic cells (DCs) at fever temperatures, the Th2 switch was abrogated via increased production of IL12 from DCs at fever temperatures. Thus, immune cells directly sense fever temperatures with likely complex physiological consequences.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.