Temperature regulates NF-κB dynamics and function through timing of A20 transcription

Area of Science:

• Immunology
• Cellular Biology
• Systems Biology

Background:

• Nuclear factor-kappa B (NF-κB) signaling is crucial for regulating inflammatory responses.
• Understanding how physiological temperature variations impact NF-κB dynamics is essential for comprehending inflammatory control.

Purpose of the Study:

• To investigate the effects of temperature fluctuations within the mammalian physiological range (34 °C to 40 °C) on NF-κB signaling dynamics and function.
• To elucidate the molecular mechanisms underlying temperature sensitivity in NF-κB pathways.

Main Methods:

• Utilized TNFα stimulation in mammalian cells to analyze NF-κB nuclear/cytoplasmic oscillations.
• Employed mathematical modeling to predict and validate the role of A20 in temperature sensitivity.
• Assessed the expression patterns of NF-κB target genes at different temperatures.

Main Results:

• Increased temperature accelerated NF-κB oscillation frequency post-TNFα stimulation.
• A20 was identified as a key mediator of temperature sensitivity; A20 silencing abolished this effect.
• Early NF-κB target gene expression timing was highly temperature-dependent, while later gene expression showed temperature compensation.

Conclusions:

• NF-κB signaling dynamics and target gene expression are significantly modulated by temperature within the physiological range.
• Temperature acts as a critical factor influencing the information transmitted by NF-κB signaling to control inflammation.
• NF-κB cross-talk with cell-fate pathways is also temperature- and TNFα-regulated, highlighting complex cellular responses.