L-arginine-dependent epigenetic regulation of interleukin-10, but not transforming growth factor-β, production by neonatal regulatory T lymphocytes

Hong Ren Yu, Ching Chang Tsai, Ling Sai Chang, Hsin Chun Huang, Hsin Hsin Cheng, Jiu Yao Wang, Jiunn Ming Sheen, Ho Chang Kuo, Kai Sheng Hsieh, Ying Hsien Huang, Kuender D. Yang*, Te Yao Hsu

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

24 Scopus citations


A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.

Original languageEnglish
Article number487
JournalFrontiers in Immunology
Issue numberAPR
StatePublished - 25 04 2017

Bibliographical note

Publisher Copyright:
© 2017 Yu, Tsai, Chang, Huang, Cheng, Wang, Sheen, Kuo, Hsieh, Huang, Yang and Hsu.


  • DNA hypomethylation
  • Interleukin-10
  • L-arginine
  • Neonate
  • Regulatory T-cells


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