NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35767626.
- Also identified by DOI 10.1126/sciadv.abo0183 and PMC identifier 9242588.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>regs</sub>) and a critical determinant of immune tolerance. Phenotypically, NAC1<sup>-/-</sup> mice showed substantial tolerance to the induction of autoimmunity and generated a larger amount of CD4<sup>+</sup> T<sub>regs</sub> 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<sub>regs</sub> with the proinflammatory cytokines interleukin-1β or tumor necrosis factor-α induced a robust up-regulation of NAC1 but evident down-regulation of FoxP3 as well as the acetylated FoxP3. These findings imply that NAC1 acts as a trigger of the immune response through destabilization of T<sub>regs</sub> and suppression of tolerance induction, and targeting of NAC1 warrants further exploration as a potential tolerogenic strategy for treatment of autoimmune disorders.