Vitamin D and IFN-β Modulate the Inflammatory Gene Expression Program of Primary Human T Lymphocytes

Front Immunol. 2020 Dec 4:11:566781. doi: 10.3389/fimmu.2020.566781. eCollection 2020.

Abstract

IFN-β treatment is a commonly used therapy for relapsing-remitting multiple sclerosis (MS), while vitamin D deficiency correlates with an increased risk of MS and/or its activity. MS is a demyelinating chronic inflammatory disease of the central nervous system, in which activated T lymphocytes play a major role, and may represent direct targets of IFN-β and vitamin D activities. However, the underlying mechanism of action of vitamin D and IFN-β, alone or in combination, remains incompletely understood, especially when considering their direct effects on the ability of T lymphocytes to produce inflammatory cytokines. We profiled the expression of immune-related genes and microRNAs in primary human T lymphocytes in response to vitamin D and IFN-β, and we dissected the impact of these treatments on cytokine production and T cell proliferation. We found that the treatments influenced primarily memory T cell plasticity, rather than polarization toward a stable phenotype. Moreover, our data revealed extensive reprogramming of the transcriptional output of primary T cells in response to vitamin D and IFN-β and provide the bases for further mechanistic insights into these commonly used treatments.

Keywords: IFN-β; gene expression; human T lymphocytes; microRNAs; plasticity; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / genetics
  • Interferon-beta / pharmacology*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Vitamin D / pharmacology*
  • Vitamins / pharmacology*

Substances

  • Vitamins
  • Vitamin D
  • Interferon-beta