Regulatory T cell immunosuppressive function requires chaperone-mediated autophagy.
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 m
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Research summary
Chaperone-mediated autophagy in regulatory T cells is required for their immunosuppressive function and the maintenance of immune tolerance. This paper is relevant because it identifies a specific cellular mechanism (CMA) that declines with age and contributes to systemic inflammation and reduced lifespan, addressing a root cause of immunosenescence rather than just treating a symptom. However, the impact is low because the findings are largely confirmatory of known Treg biology and do not propose a novel, broadly applicable intervention for extending lifespan in humans.
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