Abstract
The field that links immunity and metabolism is rapidly expanding. Apparently, non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation, suggesting that metabolic alterations can be induced by or be a consequence of an altered self-immune tolerance. In this context, a key role is played by signaling systems acting as metabolic “sensors” linking energy/nutritional status to regulatory T (Treg) cell functions. We propose that a dynamic/oscillatory activity of intracellular metabolism, through mTOR modulation, might represent a shift in understanding the molecular mechanisms governing Treg cell tolerance. In particular, the decision between Treg cell proliferation and hyporesponsiveness arises from their ability to probe the extracellular milieu and, modulating the metabolic intracellular signaling, to determine different qualitative and quantitative functional outcomes.
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Acknowledgments
G.M. is supported by grants from the EU Ideas Programme, ERC-Starting Independent Grant “LeptinMS” n. 202579, Telethon-JDRF Grant n. GJT08004 and FIRB MERIT Grant n. RBNE08HWLZ. The authors wish to thank Dr. Fortunata Carbone for the artwork and critical reading of the manuscript. This work is dedicated to the memory of Eugenia Papa and Serafino Zappacosta.
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Procaccini, C., Matarese, G. Regulatory T cells, mTOR kinase, and metabolic activity. Cell. Mol. Life Sci. 69, 3975–3987 (2012). https://doi.org/10.1007/s00018-012-1058-6
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DOI: https://doi.org/10.1007/s00018-012-1058-6