Ascorbic acid modulates immune responses through Jumonji-C domain containing histone demethylases and Ten eleven translocation (TET) methylcytosine dioxygenase

Bioessays. 2023 Nov;45(11):e2300035. doi: 10.1002/bies.202300035. Epub 2023 Sep 11.

Abstract

Ascorbic acid is a redox regulator in many physiological processes. Besides its antioxidant activity, many intriguing functions of ascorbic acid in the expression of immunoregulatory genes have been suggested. Ascorbic acid acts as a co-factor for the Fe+2 -containing α-ketoglutarate-dependent Jumonji-C domain-containing histone demethylases (JHDM) and Ten eleven translocation (TET) methylcytosine dioxygenasemediated epigenetic modulation. By influencing JHDM and TET, ascorbic acid facilitates the differentiation of double negative (CD4- CD8- ) T cells to double positive (CD4+ CD8+ ) T cells and of T-helper cells to different effector subsets. Ascorbic acid modulates plasma cell differentiation and promotes early differentiation of hematopoietic stem cells (HSCs) to NK cells. These findings indicate that ascorbic acid plays a significant role in regulating both innate and adaptive immune cells, opening up new research areas in Immunonutrition. Being a water-soluble vitamin and a safe micro-nutrient, ascorbic acid can be used as an adjunct therapy for many disorders of the immune system.

Keywords: Ascorbic acid; Epigenetic modifications; Immunomodulation; Jumonji-C domain-containing histone demethylase (JHDM); Ten eleven translocation (TET) methylcytosine dioxygenase.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine
  • Ascorbic Acid* / metabolism
  • Ascorbic Acid* / pharmacology
  • DNA Methylation
  • Dioxygenases* / genetics
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism
  • Immunity
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism

Substances

  • Ascorbic Acid
  • Jumonji Domain-Containing Histone Demethylases
  • Dioxygenases
  • Histone Demethylases
  • 5-Methylcytosine