Neural representation of cytokines by vagal sensory neurons

Tomás S. Huerta, Adrian C. Chen, Saher Chaudhry, Aisling Tynan, Timothy Morgan, Kicheon Park, Richard Adamovich-Zeitlin, Bilal Haider, Jian Hua Li, Mitali Nagpal, Stavros Zanos, Valentin A. Pavlov, Michael Brines, Theodoros P. Zanos, Sangeeta S. Chavan, Kevin J. Tracey () and Eric H. Chang ()
Additional contact information
Tomás S. Huerta: Northwell Health
Adrian C. Chen: Northwell Health
Saher Chaudhry: Northwell Health
Aisling Tynan: Northwell Health
Timothy Morgan: Northwell Health
Kicheon Park: Northwell Health
Richard Adamovich-Zeitlin: Northwell Health
Bilal Haider: Northwell Health
Jian Hua Li: Northwell Health
Mitali Nagpal: Northwell Health
Stavros Zanos: Northwell Health
Valentin A. Pavlov: Northwell Health
Michael Brines: Northwell Health
Theodoros P. Zanos: Northwell Health
Sangeeta S. Chavan: Northwell Health
Kevin J. Tracey: Northwell Health
Eric H. Chang: Northwell Health

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract The nervous system coordinates with the immune system to detect and respond to harmful stimuli. Inflammation is a universal response to injury and infection that involves the release of cytokines. While it is known that information about cytokines is transmitted from the body to the brain, how the nervous system encodes specific cytokines in the form of neural activity is not well understood. Using in vivo calcium imaging, we show that vagal sensory neurons within the nodose ganglia exhibit distinct real-time neuronal responses to inflammatory cytokines. Some neurons respond selectively to individual cytokines, while others encode multiple cytokines with distinct activity patterns. In male mice with induced colitis, inflammation increased the baseline activity of these neurons but decreased responsiveness to specific cytokines, reflecting altered neural excitability. Transcriptomic analysis of vagal ganglia from colitis mice revealed downregulation of cytokine signaling pathways, while neuronal activity pathways were upregulated. Thus, nodose ganglia neurons perform real-time encoding of cytokines at the first neural station in a body-brain axis, providing a new framework for studying the dynamic nature of neuroimmune communication.

Date: 2025
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DOI: 10.1038/s41467-025-59248-6

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