Abstract
The peripheral immune system communicates with the brain through complex anatomical routes involving the skull, the brain borders, circumventricular organs and peripheral nerves. These immune–brain communication pathways were classically considered to be dormant under physiological conditions and active only in cases of infection or damage. Yet, peripheral immune cells and signals are key in brain development, function and maintenance. In this Perspective, we propose an alternative framework for understanding the mechanisms of immune–brain communication. During brain development and in homeostasis, these anatomical structures allow selected elements of the peripheral immune system to affect the brain directly or indirectly, within physiological limits. By contrast, in ageing and pathological settings, detrimental peripheral immune signals hijack the existing communication routes or alter their structure. We discuss why a diversity of communication channels is needed and how they work in relation to one another to maintain homeostasis of the brain.
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Acknowledgements
We thank the members of Deczkowska lab for discussions and apologize to colleagues whose work was discussed without citation owing to space constraints. The Deczkowska lab for Brain-Immune Communication is supported by G5 funding from Institut Pasteur, the European Research Council Starting grant (BrainGate), Agence Nationale de la Recherche (ANR-PRC), Ville de Paris EMERGENCE(S) grant, Alzheimer’s Association Research Grant (AARG-22-917964) and Fédération pour la Recherche sur le Cerveau and Don Explore AD (Programme Explore de l’Institut Pasteur). Our lab is part of the DIM C-BRAINS, funded by the Conseil Régional d’Île-de-France. A.D.-B. is supported by Paris Region Fellowship Programme.
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Kovacs, M., Dominguez-Belloso, A., Ali-Moussa, S. et al. Immune control of brain physiology. Nat Rev Immunol 25, 515–527 (2025). https://doi.org/10.1038/s41577-025-01129-6
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DOI: https://doi.org/10.1038/s41577-025-01129-6
