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Published in Neuron - 26 May 2023

Jagot F, Gaston-Breton R, Choi AJ, Pascal M, Bourhy L, Dorado-Doncel R, Conzelmann KK, Lledo PM, Lepousez G, Eberl G

Link to Pubmed [PMID] – 37279750

Link to DOI – 10.1016/j.neuron.2023.05.009

Neuron 2023 May; ():

The central nervous system regulates systemic immune responses by integrating the physiological and behavioral constraints faced by an individual. Corticosterone (CS), the release of which is controlled in the hypothalamus by the paraventricular nucleus (PVN), is a potent negative regulator of immune responses. Using the mouse model, we report that the parabrachial nucleus (PB), an important hub linking interoceptive afferent information to autonomic and behavioral responses, also integrates the pro-inflammatory cytokine IL-1β signal to induce the CS response. A subpopulation of PB neurons, directly projecting to the PVN and receiving inputs from the vagal complex (VC), responds to IL-1β to drive the CS response. Pharmacogenetic reactivation of these IL-1β-activated PB neurons is sufficient to induce CS-mediated systemic immunosuppression. Our findings demonstrate an efficient brainstem-encoded modality for the central sensing of cytokines and the regulation of systemic immune responses.