NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance. Academic Article uri icon

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 (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-1 or tumor necrosis factor- 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.

published proceedings

  • Sci Adv

author list (cited authors)

  • Yang, J., Ren, Y., Kumar, A., Xiong, X., Das, J. K., Peng, H., ... Song, J.

complete list of authors

  • Yang, Jin-Ming||Ren, Yijie||Kumar, Anil||Xiong, Xiaofang||Das, Jugal Kishore||Peng, Hao-Yun||Wang, Liqing||Ren, Xingcong||Zhang, Yi||Ji, Cheng||Cheng, Yan||Zhang, Li||Alaniz, Robert C||de Figueiredo, Paul||Fang, Deyu||Zhou, Hongwei||Liu, Xiaoqi||Wang, Jianlong||Song, Jianxun

publication date

  • January 1, 2022 11:11 AM