Central neurons encode interleukin-1β signals and mediate stress-induced inflammation

Area of Science:

• Neuroscience
• Immunology
• Physiology

Background:

• The brain's capacity to remember and replicate inflammatory responses is known.
• Specific neural circuits activated by individual cytokines remain unidentified.

Purpose of the Study:

• To investigate how the brain encodes inflammatory signals from interleukin-1 beta (IL-1β).
• To identify the specific neural circuits involved in mediating IL-1β-induced physiological responses.

Main Methods:

• Brain-wide response mapping to IL-1β.
• Targeted recombination in active populations, single-nucleus RNA sequencing (snRNA-seq), and circuit tracing.
• Chemogenetics to reactivate specific neuronal populations.

Main Results:

• IL-1β prominently engaged the bed nucleus of the stria terminalis (BNST).
• Corticotropin-releasing hormone-expressing BNST neurons were identified as encoding IL-1β signals.
• Reactivation of these BNST neurons mimicked IL-1β effects, increasing IL-6, corticosterone, and heart rate via a specific neural pathway.
• Restraint stress activated the same BNST neurons, producing similar physiological outcomes.

Conclusions:

• A specific neural circuit, involving BNST neurons, mediates systemic responses to IL-1β.
• This circuit's activation by both IL-1β and stress provides insight into neuroimmune interactions.
• Findings offer mechanistic understanding relevant to stress and inflammatory diseases.