Retinoic acid modulates hyperactive T cell responses and protects Vitamin A deficient mice against persistent lymphocytic choriomeningitis virus infection

Yuejin Liang, Panpan Yi, Xiaofang Wang, Biao Zhang, Zuliang Jie, Lynn Soong, Jiaren Sun

Research output: Contribution to journalArticle

Abstract

Vitamin A deficiency (VAD) is a major public health problem and is associated with increased host susceptibility to infection; however, how VAD influences viral infection remains unclear. Using a persistent lymphocytic choriomeningitis virus infection model, we showed in this study that although VAD did not alter innate type I IFN production, infected VAD mice had hyperactive, virus-specific T cell responses at both the acute and contraction stages, showing significantly decreased PD-1 but increased cytokine (IFN-g, TNF-a, and IL-2) expression by T cells. Compared with control mice, VAD mice displayed excessive inflammation and more severe liver pathology, with increased death during persistent infection. Of note, supplements of all-trans retinoic acid (RA), one of the important metabolites of vitamin A, downregulated hyperactive T cell responses and rescued the persistently infected VAD mice. By using adoptive transfer of splenocytes, we found that the environmental vitamin A or its metabolites acted as rheostats modulating antiviral T cells. The analyses of T cell transcriptional factors and signaling pathways revealed the possible mechanisms of RA, as its supplements inhibited the abundance of NFATc1 (NFAT 1), a key regulator for T cell activation. Also, following CD3/CD28 cross-linking stimulation, RA negatively regulated the TCR-proximal signaling in T cells, via decreased phosphorylation of Zap70 and its downstream signals, including phosphorylated AKT, p38, ERK, and S6, respectively. Together, our data reveal VAD-mediated alterations in antiviral T cell responses and highlight the potential utility of RA for modulating excessive immune responses and tissue injury in infectious diseases.

Original languageEnglish (US)
Pages (from-to)2984-2994
Number of pages11
JournalJournal of Immunology
Volume204
Issue number11
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Retinoic acid modulates hyperactive T cell responses and protects Vitamin A deficient mice against persistent lymphocytic choriomeningitis virus infection'. Together they form a unique fingerprint.

  • Cite this