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Updated: Aug 6, 2026

Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
Regulatory T cell immunosuppressive function requires chaperone-mediated autophagy
Ranee Harrison1, Floralba Gjergjova2, Susmita Kaushik2,3
1Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
Abstract:
Regulatory T cells (Tregs) are essential for maintaining immune tolerance. We recently identified chaperone-mediated autophagy (CMA), a selective lysosomal degradation pathway, as a critical regulator of Treg function. Treg activation induces CMA, but this response is markedly diminished with aging. Mice lacking CMA specifically in Tregs develop systemic inflammation, impaired immune tolerance and reduced lifespan. We confirm that CMA is a fundamental mechanism supporting Treg suppressive function as CMA-deficient Tregs are unable to suppress intestinal inflammation in a model of inflammatory bowel disease and fail to block the anti-oncogenic immune response activated in a syngeneic tumor model. Mechanistically, CMA supports metabolic fitness, remodels immune-related protein networks, and promotes degradation of the m6A RNA demethylase FTO, linking lysosomal proteostasis to epitranscriptomic control of IL-2 responsiveness. Restoration of CMA in aged mice improves Treg function, highlighting CMA as a promising therapeutic target for both inflammatory diseases and cancer immunotherapy.
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