Work

c-Rel is a thermo-responsive knob that tunes fibroblast NF-κB signaling

Year: 2026

Type: article

Abstract: Thermal regulation is a mechanism for warm-blooded animals to maintain homeostasis against ambient temperature stress. Also, core body temperature rises with fever, an integral part of host responses to infection. Although responses to heat or cold shock have been described, little is understood about how physiological temperature variations affect inflammatory responses. We tracked real-time responses of NF-κB RelA and c-Rel transcription factors to inflammatory and pyrogenic cytokines TNF-α or IL-1β using endogenous knock-in reporter fibroblasts in temperatures ranging from 24°C to 40°C. Quantitative live-cell imaging showed that c-Rel signaling, but not RelA, increases with rising temperature. Computational modeling and transcriptomic analysis indicate that the divergent signaling behaviors of these canonical NF-κB subunits cannot be explained solely by accelerated biochemical reactions in higher temperatures. Rather, cytokine receptor-proximal adaptors are likely to amplify c-Rel signaling for precise analog behaviors. The temperature-sensitivity of fibroblast c-Rel has implications for inflammatory cascades in elevated temperatures.

Source: iScience

DOI: 10.1016/j.isci.2026.117308

Authors: Yeuran Oh, Shah Md Toufiqur Rahman, Kyu-Seon Oh, Daisy Dahiya, Myong-Hee Sung

Institutions: National Institutes of Health, National Institute on Aging

Language: English

Topic: NF-κB Signaling Pathways

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,240

Funders: National Institutes of Health, National Institute on Aging