Tui Na Acupressure Modulates Treg Immunosuppression via FoxP3/mTORC1 Signalling in ALS Mice.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease driven by neuroinflammation, where regulatory T cell (Treg) dysfunction exacerbates immune imbalance. This study explores whether Tui Na acupressure, a traditional Chinese therapy, can restore Treg immunosuppressive function through the FoxP3/mTORC1 signalling pathway to mitigate ALS pathology. In SOD1G93A ALS mice, Tui Na was applied at the Shenshu acupoint, with motor and cognitive functions assessed via rotarod, tail suspension, novel object recognition, and Y-maze tests. Multi-omics (transcriptomics, proteomics), flow cytometry, ELISA, and Western blot analysed Treg proportions, cytokine profiles, and pathway activation. In vitro assays evaluated Treg proliferation and immunosuppression. Tui Na significantly enhanced motor and cognitive performance, increased Treg proportions in spleen, lymph nodes, and blood, and elevated anti-inflammatory cytokines (IL-10, TGF-β) while reducing pro-inflammatory markers (IL-6, TNF-α). Transcriptomic and proteomic analyses revealed upregulated FoxP3, Mtor, and Raptor, with enhanced Treg proliferation and immunosuppression confirmed in vitro. Pathway inhibitors (GSK126, rapamycin) reversed these effects, confirming FoxP3/mTORC1 dependency. Tui Na also reduced apoptosis and oxidative stress, supporting immune regulation. These findings highlight Tui Na's potential to restore Treg-mediated immune balance in ALS, offering a non-pharmacological therapeutic strategy. This study provides novel immunological insights into Tui Na's mechanisms, advocating its clinical evaluation for ALS and related immune-driven disorders.