Journal Article

DZNE-2026-00577

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Long-term rapamycin treatment suppresses IL-17-producing gamma delta T cells and blunts neuroinflammation in aging.

Torrent, C. (First author)DZNE* ; Gagliardi, C.DZNE* ; Fülle, N.DZNE* ; Antignano, I.DZNE* ; Bernis, M. E.DZNE* ; Stork, M.DZNE* ; Bano, D.DZNE* ; Capasso, M.DZNE* ; Keane, L. (Last author)DZNE*

2026
PLOS San Francisco, California, US

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Please use a persistent id in citations: doi:10.1371/journal.pone.0343183

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.

Keyword(s): Animals (MeSH) ; Sirolimus: pharmacology (MeSH) ; Sirolimus: administration & dosage (MeSH) ; Interleukin-17: metabolism (MeSH) ; Aging: immunology (MeSH) ; Aging: drug effects (MeSH) ; Mice (MeSH) ; Microglia: drug effects (MeSH) ; Microglia: immunology (MeSH) ; Microglia: metabolism (MeSH) ; Receptors, Antigen, T-Cell, gamma-delta: metabolism (MeSH) ; Neuroinflammatory Diseases: drug therapy (MeSH) ; Neuroinflammatory Diseases: immunology (MeSH) ; Inflammation: drug therapy (MeSH) ; Male (MeSH) ; Mice, Inbred C57BL (MeSH) ; Intraepithelial Lymphocytes: drug effects (MeSH) ; Intraepithelial Lymphocytes: immunology (MeSH) ; Intraepithelial Lymphocytes: metabolism (MeSH) ; T-Lymphocytes: drug effects (MeSH) ; T-Lymphocytes: immunology (MeSH) ; T-Lymphocytes: metabolism (MeSH) ; Immunosuppressive Agents: pharmacology (MeSH) ; Sirolimus ; Interleukin-17 ; Receptors, Antigen, T-Cell, gamma-delta ; Immunosuppressive Agents

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Contributing Institute(s):

1. Immune Regulation (AG Capasso)
2. Neonatal Neuroscience (AG Sabir)
3. Nuclear Function in CNS Pathophysiology (AG Salomoni)
4. Aging and Neurodegeneration (AG Bano)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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