The mTOR pathway orchestrates diverse physiological processes, including T cell functions and fate decisions; however, the regulation of mTOR-dependent T cell differentiation remains elusive. In this issue, Park et al. examine the role of TSC1, an mTOR signaling regulator, in T cell differentiation and the balance between T cell–mediated immunity and tolerance. They found that enhanced mTOR activity in Tsc1-deficient T cells promotes Th1 and Th17 differentiation, leading to increased intestinal inflammation in murine colitis. Tsc1-deficient Tregs had impaired suppressive activity in inflammatory conditions. These defects were associated with the acquisition of effector-like phenotypes and could be further exacerbated by concomitant loss of transcription factor Foxo3. This study highlights that TSC1-mediated control of mTOR activity impinges on the balance between immunity and tolerance by dictating effector and regulatory T cell responses.
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