Expression of NAC1 Restrains the Memory Formation of CD8+ T Cells during Viral Infection

Liqing Wang, Anil Kumar, Jugal Kishore Das, Yijie Ren, Hao Yun Peng, Darby Jane Ballard, Xiaofang Xiong, Jacob Rance Davis, Xingcong Ren, Jin Ming Yang, Jianxun Song

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Nucleus accumbens-associated protein 1 (NAC1) is a transcription co-factor that has been shown to possess multiple roles in stem cell and cancer biology. However, little is known about its roles in regulation of the immune system. In the current study, we observed that expression of NAC1 impacted the survival of CD8+ T cells in vitro. NAC1−/− CD8+ T cells displayed lower metabolism, including reduced glycolysis and oxidative phosphorylation. In vivo, compared with wild-type (WT) mice, NAC1−/− mice produced a lower response to vaccinia virus (VACV) infection, and viral antigen (Ag)-specific CD8+ T cells decreased more slowly. Additionally, we observed that the NAC1−/− mice demonstrated a stronger memory formation of viral Ag-specific CD8+ T cells post-viral infection. Mechanically, we identified that compared with WT CD8+ T cells, the Interferon Regulatory Factor 4 (IRF4), a key transcription factor in T cell development, was highly expressed in NAC1−/− CD8+ T cells, insinuating that IRF4 could be a critical regulatory target of NAC1 in the memory formation of CD8+ T cells. Our results indicate that NAC1 restrains the memory formation of CD8+ T cells by modulating IRF4, and targeting NAC1 may be exploited as a new approach to boosting CD8+ T cell memory.

Original languageEnglish
Article number1713
JournalViruses
Volume14
Issue number8
DOIs
StatePublished - Aug 2022

Bibliographical note

Funding Information:
This work was supported by National Cancer Institute Grant R01CA221867 to J.Y. and J.S., and National Institutes of Health Grant R01AI121180 and R21AI167793, and Department of Defense Grant LC210150 to J.S.

Publisher Copyright:
© 2022 by the authors.

Keywords

  • CD8 T cell memory
  • IRF4
  • NAC1
  • vaccinia virus

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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