NAC1 confines virus-specific memory formation of CD4+ T cells through the ROCK1-mediated pathway. Academic Article uri icon


  • Nucleus accumbens-associated protein 1 (NAC1), a transcriptional cofactor, has been found to play important roles in regulating regulatory T cells, CD8+ T cells, and antitumor immunity, but little is known about its effects on T-cell memory. In this study, we found that NAC1 expression restricts memory formation of CD4+ T cells during viral infection. Analysis of CD4+ T cells from wild-type (WT) and NAC1-deficient (-/- ) mice showed that NAC1 is essential for T-cell metabolism, including glycolysis and oxidative phosphorylation, and supports CD4+ T-cell survival in vitro. We further demonstrated that a deficiency of NAC1 downregulates glycolysis and correlates with the AMPK-mTOR pathway and causes autophagy defective in CD4+ T cells. Loss of NAC1 reduced the expression of ROCK1 and the phosphorylation and stabilization of BECLIN1. However, a forced expression of ROCK1 in NAC1-/- CD4+ T cells restored autophagy and the activity of the AMPK-mTOR pathway. In animal experiments, adoptively transferred NAC1-/- CD4+ T cells or NAC1-/- mice challenged with VACV showed enhanced formation of VACV-specific CD4+ memory T cells compared to adoptively transferred WT CD4+ T cells or WT mice. This memory T-cell formation enhancement was abrogated by forcing expression of ROCK1. Our study reveals a novel role for NAC1 as a suppressor of CD4+ T-cell memory formation and suggests that targeting NAC1 could be a new approach to promoting memory CD4+ T-cell development, which is critical for an effective immune response against pathogens.

published proceedings

  • J Med Virol

author list (cited authors)

  • Wang, L., Peng, H., Kishore Das, J., Kumar, A., Ren, Y., Ballard, D. J., ... Song, J.

complete list of authors

  • Wang, Liqing||Peng, Hao-Yun||Kishore Das, Jugal||Kumar, Anil||Ren, Yijie||Ballard, Darby J||Xiong, Xiaofang||Yang, Wen||Ren, Xingcong||de Figueiredo, Paul||Yang, Jin-Ming||Song, Jianxun

publication date

  • July 2023