| First Author | Yang JM | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 26 | Pages | eabo0183 |
| PubMed ID | 35767626 | Mgi Jnum | J:326773 |
| Mgi Id | MGI:7313697 | Doi | 10.1126/sciadv.abo0183 |
| Citation | Yang JM, et al. (2022) NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance. Sci Adv 8(26):eabo0183 |
| abstractText | 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 (Tregs) 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(+) Tregs 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 Tregs with the proinflammatory cytokines interleukin-1beta or tumor necrosis factor-alpha 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 Tregs and suppression of tolerance induction, and targeting of NAC1 warrants further exploration as a potential tolerogenic strategy for treatment of autoimmune disorders. |
