Long-term rapamycin treatment suppresses IL-17-producing gamma delta T cells and blunts neuroinflammation in aging
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Date
2026-05-28
Authors
Torrent, Clement
Gagliardi, Caterina
Fülle, Nina
Antignano, Ignazio
Bernis, Maria Eugenia
Stork, Miriam
Bano, Daniele
Capasso, Melania
Keane, Lily
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Abstract
Aging is the gradual accumulation of structural and functional changes in an organism over time, including immune remodeling and a progressive increase in basal inflammation, or inflammaging. The mTOR pathway is a central driver of aging-related diseases, such as cancer, chronic inflammation and neurodegeneration; pharmacological inhibition with rapamycin is associated with reduced aged-related morbidity and increased lifespan across species. Nonetheless, concerns remain about the use of rapamycin, a well-established immunosuppressant in transplant medicine, as an anti-aging intervention. Here, we evaluated the impact of prolonged low-dose dietary rapamycin on the aging immune system. Treatment did not significantly alter innate or adaptive immune cell populations, including brain resident microglia; however, it attenuated the age-associated accumulation of IL-17–producing γδ T cells, particularly in the peritoneal cavity. After a peripheral inflammatory LPS challenge, circulating IL-17 levels were significantly reduced and correlated with an attenuation of microglia inflammatory phenotype. These findings suggest that prolonged low-dose rapamycin exposure exerts minor systemic immune changes, while selectively limiting age-related γδ T cell expansion and neuroinflammation associated with systemic inflammation.
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© 2026, Torrent et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords
SDG 3 - Good Health and Well-being , Long-term rapamycin treatment , mTOR pathway , Low-dose dietary rapamycin , Neuroinflammation , [Medicine] , [APCMicrobiome] , Multidisciplinary
Citation
Torrent, C, Gagliardi, C, Fülle, N, Antignano, I, Bernis, M E, Stork, M, Bano, D, Capasso, M & Keane, L 2026, 'Long-term rapamycin treatment suppresses IL-17-producing gamma delta T cells and blunts neuroinflammation in aging', PLOS ONE, vol. 21, no. 5, e0343183, pp. 1-17. https://doi.org/10.1371/journal.pone.0343183
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