RESEARKA

Mechanistically, rapamycin's immunomodulatory effects operate through distinct pathways depending on tissue context and disease state. Preclinical data suggest that chronic mTOR inhibition reshapes the immune landscape by simultaneously affecting adaptive and innate immune compartments while altering the gut microbiome composition (Hurez 2015). In inflammatory liver disease, rapamycin suppresses NF-κB signaling by enhancing the physical interaction between p65 and its inhibitor IκBα, representing a direct anti-inflammatory mechanism (Ge 2023). The mechanistic substrate underlying the cardiac protection observed in autoimmune myocarditis involves mTORC1-dependent reprogramming of macrophages through the C/EBPβ–OSM axis, specifically targeting Cxcl9+ macrophage subsets (Zhuang 2025). At the signaling level, rapamycin shares regulatory mechanisms over MAPK pathways with other longevity-associated compounds, suggesting convergence on intracellular inflammatory signaling networks (Wink 2022).

Citation Support

• source_1 Moel 2025
• source_2 Gkioni 2025
• source_3 Smiaek 2023
• source_4 Willows 2023
• source_5 Harinath 2025