TY - JOUR
T1 - NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance
AU - Yang, Jin Ming
AU - Ren, Yijie
AU - Kumar, Anil
AU - Xiong, Xiaofang
AU - Das, Jugal Kishore
AU - Peng, Hao Yun
AU - Wang, Liqing
AU - Ren, Xingcong
AU - Zhang, Yi
AU - Ji, Cheng
AU - Cheng, Yan
AU - Zhang, Li
AU - Alaniz, Robert C.
AU - De Figueiredo, Paul
AU - Fang, Deyu
AU - Zhou, Hongwei
AU - Liu, Xiaoqi
AU - Wang, Jianlong
AU - Song, Jianxun
N1 - Publisher Copyright:
© 2022 American Association for the Advancement of Science. All rights reserved.
PY - 2022/7
Y1 - 2022/7
N2 - 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-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 Tregs and suppression of tolerance induction, and targeting of NAC1 warrants further exploration as a potential tolerogenic strategy for treatment of autoimmune disorders.
AB - 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-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 Tregs and suppression of tolerance induction, and targeting of NAC1 warrants further exploration as a potential tolerogenic strategy for treatment of autoimmune disorders.
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U2 - 10.1126/sciadv.abo0183
DO - 10.1126/sciadv.abo0183
M3 - Article
C2 - 35767626
AN - SCOPUS:85133214080
VL - 8
JO - Science advances
JF - Science advances
IS - 26
M1 - eabo0183
ER -