Vitamin D deficiency contributes to the reduction and impaired function of naïve CD45RA⁺ regulatory T cell in chronic heart failure

J Immunol Res. 2015:2015:547697. doi: 10.1155/2015/547697. Epub 2015 Apr 23.

Abstract

The effect of vitamin D pertinent to cardiovascular health on the heart itself is considered to shift toward an anti-inflammatory response in chronic heart failure (CHF); however, its underlying mechanism is not completely understood. In this study, we demonstrated that plasma 25(OH)D level, negatively associated with NT-ProBNP, correlated with the decreased Treg in CHF compared to the patients with other cardiovascular diseases and healthy and older donors. Naïve Treg cell (CD4(+)CD45RA(+)Foxp3(lo)T) subset, rather than whole Treg cells, contributes to the reduction of Treg in CHF. 1,25(OH)2D treatment maintained partial expression of CD45RA on CD4(+)T cell after αCD3/CD28 monoclonal antibodies activation and ameliorated the impaired CD4(+)CD45RA(+)T cell function from CHF patients through upregulating Foxp3 expression and IL-10 secretion in vitro. Low level of vitamin D receptor (VDR) was detected in CD4(+)CD45RA(+)T cell of CHF than control, while 1,25(OH)2D treatment increased the VDR expression to exert its immunosuppression on T cell. The results of this study might provide tangible evidence to our knowledge of the impact of vitamin D supplementation on naïve Tregs, which may offer new means of preventing and treating CHF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D 2 / blood
  • 25-Hydroxyvitamin D 2 / metabolism
  • 25-Hydroxyvitamin D 2 / pharmacology*
  • Aged
  • Anti-Inflammatory Agents / metabolism
  • CD4 Antigens / metabolism
  • Female
  • Flow Cytometry
  • Heart Failure / immunology*
  • Heart Failure / pathology
  • Humans
  • Inflammation / immunology
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-17 / blood
  • Leukocyte Common Antigens / metabolism
  • Lymphocyte Count
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*
  • Vitamin D Deficiency / pathology*

Substances

  • Anti-Inflammatory Agents
  • CD4 Antigens
  • IL10 protein, human
  • IL17A protein, human
  • Interleukin-17
  • Interleukin-10
  • 25-Hydroxyvitamin D 2
  • Interferon-gamma
  • Leukocyte Common Antigens