Vitamin C promotes maturation of T-cells

Jared Manning, Birgitta Mitchell, Daniel A. Appadurai, Arvind Shakya, Laura Jean Pierce, Hongfang Wang, Vincent Nganga, Patrick Swanson, James M. May, Dean Tantin, Gerald J. Spangrude

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Aims: Vitamin C (ascorbic acid) is thought to enhance immune function, but the mechanisms involved are obscure. We utilized an in vitro model of T-cell maturation to evaluate the role of ascorbic acid in lymphocyte development. Results: Ascorbic acid was essential for the developmental progression of mouse bone marrow-derived progenitor cells to functional T-lymphocytes in vitro and also played a role in vivo. Ascorbate-mediated enhancement of T-cell development was lymphoid cell-intrinsic and independent of T-cell receptor (TCR) rearrangement. Analysis of TCR rearrangements demonstrated that ascorbic acid enhanced the selection of functional TCRαβ after the stage of β-selection. Genes encoding the coreceptor CD8 as well as the kinase ZAP70 were upregulated by ascorbic acid. Pharmacologic inhibition of methylation marks on DNA and histones enhanced ascorbate-mediated differentiation, suggesting an epigenetic mechanism of Cd8 gene regulation via active demethylation by ascorbate-dependent Fe2+ and 2-oxoglutarate-dependent dioxygenases. Innovation: We speculate that one aspect of gene regulation mediated by ascorbate occurs at the level of chromatin demethylation, mediated by Jumonji C (JmjC) domain enzymes that are known to be reliant upon ascorbate as a cofactor. JmjC domain enzymes are also known to regulate transcription factor activity. These two mechanisms are likely to play key roles in the modulation of immune development and function by ascorbic acid. Conclusion: Our results provide strong experimental evidence supporting a role for ascorbic acid in T-cell maturation as well as insight into the mechanism of ascorbate-mediated enhancement of immune function. Antioxid. Redox Signal. 19, 2054-2067.

Original languageEnglish
Pages (from-to)2054-2067
Number of pages14
JournalAntioxidants and Redox Signaling
Volume19
Issue number17
DOIs
StatePublished - Dec 10 2013

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T-cells
Ascorbic Acid
T-Lymphocytes
T-Cell Antigen Receptor
Gene expression
Lymphocytes
Genes
Dioxygenases
Gene encoding
Methylation
Enzymes
Epigenomics
Histones
Chromatin
Oxidation-Reduction
Bone
Transcription Factors
Phosphotransferases
Stem Cells
Innovation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Manning, J., Mitchell, B., Appadurai, D. A., Shakya, A., Pierce, L. J., Wang, H., ... Spangrude, G. J. (2013). Vitamin C promotes maturation of T-cells. Antioxidants and Redox Signaling, 19(17), 2054-2067. https://doi.org/10.1089/ars.2012.4988

Vitamin C promotes maturation of T-cells. / Manning, Jared; Mitchell, Birgitta; Appadurai, Daniel A.; Shakya, Arvind; Pierce, Laura Jean; Wang, Hongfang; Nganga, Vincent; Swanson, Patrick; May, James M.; Tantin, Dean; Spangrude, Gerald J.

In: Antioxidants and Redox Signaling, Vol. 19, No. 17, 10.12.2013, p. 2054-2067.

Research output: Contribution to journalArticle

Manning, J, Mitchell, B, Appadurai, DA, Shakya, A, Pierce, LJ, Wang, H, Nganga, V, Swanson, P, May, JM, Tantin, D & Spangrude, GJ 2013, 'Vitamin C promotes maturation of T-cells', Antioxidants and Redox Signaling, vol. 19, no. 17, pp. 2054-2067. https://doi.org/10.1089/ars.2012.4988
Manning J, Mitchell B, Appadurai DA, Shakya A, Pierce LJ, Wang H et al. Vitamin C promotes maturation of T-cells. Antioxidants and Redox Signaling. 2013 Dec 10;19(17):2054-2067. https://doi.org/10.1089/ars.2012.4988
Manning, Jared ; Mitchell, Birgitta ; Appadurai, Daniel A. ; Shakya, Arvind ; Pierce, Laura Jean ; Wang, Hongfang ; Nganga, Vincent ; Swanson, Patrick ; May, James M. ; Tantin, Dean ; Spangrude, Gerald J. / Vitamin C promotes maturation of T-cells. In: Antioxidants and Redox Signaling. 2013 ; Vol. 19, No. 17. pp. 2054-2067.
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