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Review
. 2018 Oct 19;46(5):1147-1159.
doi: 10.1042/BST20180169. Epub 2018 Oct 8.

Vitamin C and immune cell function in inflammation and cancer

Abel Ang  1 , Juliet M Pullar  2 , Margaret J Currie  1 , Margreet C M Vissers  3
Affiliations
Review

Vitamin C and immune cell function in inflammation and cancer

Abel Ang et al. Biochem Soc Trans. .

Abstract

Vitamin C (ascorbate) is maintained at high levels in most immune cells and can affect many aspects of the immune response. Intracellular levels generally respond to variations in plasma ascorbate availability, and a combination of inadequate intake and increased turnover during severe stress can result in low plasma ascorbate status. Intracellular ascorbate supports essential functions and, in particular, acts as an enzyme cofactor for Fe- or Cu-containing oxygenases. Newly discovered enzymes in this family regulate cell metabolism and epigenetics, and dysregulation of their activity can affect cell phenotype, growth and survival pathways, and stem cell phenotype. This brief overview details some of the recent advances in our understanding of how ascorbate availability can affect the hydroxylases controlling the hypoxic response and the DNA and histone demethylases. These processes play important roles in the regulation of the immune system, altering cell survival pathways, metabolism and functions.

Keywords: ascorbate; demethylation; hydroxylases; hypoxia inducible factors; vitamin C.

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Conflict of interest statement

The Authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1.
Figure 1.. A summary of the recently reported effects of ascorbate-dependent processes in immune cells.
(A) Effects on myeloid cells and (B) lymphoid cells. Effects shown in black font represent a reported role of HIF, TET or Jumonji demethylases, text in red indicates a reported effect of HIF, TET or Jumonji in the context of cancer and orange text indicates an effect of ascorbate on immune cells. The inter-relationships between these are indicated by arrows. References from the Figure: Achuthan 2016 [135]; Agathocleous 2017 [53]; Anderson 1980 [164]; Backer 2017 [88] Berger 2013 [101]; Beyaz 2017 [162]; Bhandari 2013 [165]; Bozonet 2015 [108]; Braverman 2016 [86]; Campbell 1999 [166]; Cimmino 2017 [142]; Colegio 2014 [90]; Cramer 2003 [84]; Cribbs 2018 [163]; Cull 2017 [131]; Dang 2011 [112]; De Santa 2009 [137]; Doedens 2010 [93]; [113]; Fluck 2016 [115]; Gaut 2006 [107]; Goldschmidt 1991 [106]; Hammami 2018 [116]; He 2016 [167]; Henke 2016 [94]; Higashiyama 2012 [114]; Huijskens 2014,2015 [122,123]; Ichiyama 2015 [148]; Imtiyaz 2010 [87]; Ishii 2009 [139]; Jeong 2011,2014 [95,96]; Johnston 1991 [168]; Kasahara 2017 [158]; Kim 2012 [169]; Ko 2015 [170]; Kruidenier 2012 [141]; LaMere 2017 [151]; Labiano 2017 [119]; Li 2014 [153]; Li 2018 [83]; Lio 2016 [171]; Liu 2015 [154]; Maeng 2008 [172]; Manning 2013 [124]; Mecklenburgh 2002 [98]; Mingay 2018 [55]; Nair 2016 [156]; Nestor 2016 [147]; Nikolouli 2017 [157]; Noh 2005 [173]; Noman 2014 [92]; Northrup 2017 [161]; Oda 2006 [82]; Orlanski 2016 [174]; Palazon 2017 [117]; Perez-Cruz 2003 [103]; Peyssonnaux 2005 [85]; Ptaschinksi 2015 [146]; Puskas 2002 [175]; Satoh 2010 [134]; Shalova 2015 [89]; Shi 2011 [111]; Shilotri 1977 [176]; Song 2017 [159]; Talks 2000 [177]; Tsagaratou 2017 [160]; Vissers 2004,2007 [178,179]; Vojdani 1993 [180]; Wallner 2016 [132]; Walmsley 2005,2006 [99,100]; Wei 2009 [152]; Yan 2014 [140]; Yildirim 2017 [136]; Yue 2016 [155]; Zhang 2014,2015 [133,145].
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