NAC1 confines virus‐specific memory formation of CD4+ T cells through the ROCK1‐mediated pathway
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 01, 2023
- Source ID
- 10.1002/jmv.28957
Entities
People
- Anil Kumar
- Darby J. Ballard
- Hao‐Yun Peng
- Jianxun Song
- Jin‐ming Yang
- Jugal Kishore Das
- Liqing Wang
- Paul de Figueiredo
- Wen Yang
- Xiaofang Xiong
- Xingcong Ren
- Yijie Ren
Organizations
- National Institutes of Health
- United States Department of Defense
- University of Kentucky