NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance.

ABSTRACT: We report here that nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the Broad-complex, Tramtrack, Bric-a-brac/poxvirus and zinc finger (BTB/POZ) gene family, is a negative regulator of FoxP3 in regulatory T cells (T_regs) and a critical determinant of immune tolerance. Phenotypically, NAC1^-/- mice showed substantial tolerance to the induction of autoimmunity and generated a larger amount of CD4⁺ T_regs that exhibit a higher metabolic profile and immune-suppressive activity, increased acetylation and expression of FoxP3, and slower turnover of this transcription factor. Treatment of T_regs with the proinflammatory cytokines interleukin-1β or tumor necrosis factor-α induced a robust up-regulation of NAC1 but evident down-

SUBMITTER: Yang JM 

PROVIDER: S-EPMC9242588 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature