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NAC1 confines virus‐specific memory formation of CD4+ T cells through the ROCK1‐mediated pathway.
- Source :
- Journal of Medical Virology; Jul2023, Vol. 95 Issue 7, p1-15, 15p
- Publication Year :
- 2023
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01466615
- Volume :
- 95
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Journal of Medical Virology
- Publication Type :
- Academic Journal
- Accession number :
- 167371800
- Full Text :
- https://doi.org/10.1002/jmv.28957