Abstract The inflammasome comprised of an innate immune receptor/sensor, pro-caspase-1, and a common adaptor molecule, ASC (apoptotic speck-containing protein with a CARD) initiates innate defense and inflammatory response by activating caspase-1 and pyroptotic cell death in myeloid cells. Consistent with their pro-inflammatory function, caspase-1, ASC and NLRP3 were known to exacerbate autoimmunity during experimental autoimmune encephalomyelitis (EAE) by enhancing IL-1b and IL-18 secretion in myeloid cells. Here we reveal an unexpected function of a DNA-binding inflammasome receptor, AIM2 (Absent in Melanoma 2), in T regulatory cells (Tregs) to restrain two models of autoimmune disease, including experimental autoimmune encephalomyelitis and T cell-mediated colitis, by studying whole-body and Treg-specific Aim2-deficient mice. AIM2 is highly expressed by human and mouse Tregs, with its expression induced by TGF-b and its promoter occupied by transcription factors associated with Tregs, including Runx1, Ets1, Bcl11b and CREB. Moreover, we demonstrate that AIM2 promotes the stability of Tregs during inflammation in lineage tracing mice. RNA-seq, biochemical and metabolic analyses revealed that AIM2 attenuates Akt-phosphorylation, mTOR, Myc and glycolysis, but promotes lipid oxidative phosphorylation in Tregs. Mechanistically, AIM2 interacts with the RACK1/PP2A-phosphatase complex to restrain Akt-phosphorylation. While AIM2 is generally accepted as an inflammasome effector in myeloid cells, this report unveils a T cell-intrinsic role of AIM2 in restraining autoimmunity by diminishing Akt-mTOR signaling and altering immune-metabolism to enhance Treg stability.