MAP7 and MUCL1 Are Biomarkers of Vitamin D3-Induced Tolerogenic Dendritic Cells in Multiple Sclerosis Patients

Front Immunol. 2019 Jun 19:10:1251. doi: 10.3389/fimmu.2019.01251. eCollection 2019.

Abstract

The administration of autologous tolerogenic dendritic cells (tolDC) has become a promising alternative for the treatment of autoimmune diseases, such as multiple sclerosis (MS). Specifically, the use of vitamin D3 for the generation of tolDC (vitD3-tolDC) constitutes one of the most widely studied approaches, as it has evidenced significant immune regulatory properties, both in vitro and in vivo. In this article, we generated human vitD3-tolDC from monocytes from healthy donors and MS patients, characterized in both cases by a semi-mature phenotype, secretion of IL-10 and inhibition of allogeneic lymphocyte proliferation. Additionally, we studied their transcriptomic profile and selected a number of differentially expressed genes compared to control mature and immature dendritic cells for their analysis. Among them, qPCR results validated CYP24A1, MAP7 and MUCL1 genes as biomarkers of vitD3-tolDC in both healthy donors and MS patients. Furthermore, we constructed a network of protein interactions based on the literature, which manifested that MAP7 and MUCL1 genes are both closely connected between them and involved in immune-related functions. In conclusion, this study evidences that MAP7 and MUCL1 constitute robust and potentially functional biomarkers of the generation of vitD3-tolDC, opening the window for their use as quality controls in clinical trials for MS.

Keywords: biomarkers; immune tolerance; multiple sclerosis; tolerogenic dendritic cells; vitamin D3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cholecalciferol* / metabolism
  • Cytokines / metabolism
  • Dendritic Cells* / immunology
  • Dendritic Cells* / metabolism
  • Disease Susceptibility
  • Humans
  • Immune Tolerance*
  • Immunohistochemistry
  • Immunophenotyping
  • Inflammation Mediators / metabolism
  • Microtubule-Associated Proteins* / metabolism
  • Mucins* / metabolism
  • Multiple Sclerosis* / etiology
  • Multiple Sclerosis* / metabolism
  • Multiple Sclerosis* / pathology
  • Signal Transduction

Substances

  • Biomarkers
  • Cholecalciferol
  • Cytokines
  • Inflammation Mediators
  • Microtubule-Associated Proteins
  • Mucins
  • MUCL1 protein, human
  • MAP7 protein, human