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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01251

MAP7 and MUCL1 are biomarkers of vitamin D3-induced tolerogenic dendritic cells in multiple sclerosis patients

 Juan Navarro-Barriuso1, 2,  Maria Jose Mansilla1, 2, Bibiana Quirant-Sánchez1, 2, Alicia Ardiaca-Martínez1, 2, Aina Teniente-Serra1, 2, Silvia Presas-Rodríguez3, 4,  Anja ten Brinke5, Cristina Ramo-Tello3, 4 and  Eva M. Martinez-Caceres1, 2*
  • 1Germans Trias i Pujol Health Science Research Institute (IGTP), Spain
  • 2Autonomous University of Barcelona, Spain
  • 3Hospital Germans Trias i Pujol, Spain
  • 4Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Barcelona, Spain
  • 5Sanquin Research, Netherlands

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: Tolerogenic dendritic cells, multiple sclerois, biomarkers, Vitamin D3, Immune Tolerance

Received: 18 Dec 2018; Accepted: 16 May 2019.

Edited by:

Piotr Trzonkowski, Medical University of Gdansk, Poland

Reviewed by:

Claudia Volpi, University of Perugia, Italy
Aurelie Moreau, Institut National de la Santé et de la Recherche Médicale (INSERM), France  

Copyright: © 2019 Navarro-Barriuso, Mansilla, Quirant-Sánchez, Ardiaca-Martínez, Teniente-Serra, Presas-Rodríguez, ten Brinke, Ramo-Tello and Martinez-Caceres. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Eva M. Martinez-Caceres, Germans Trias i Pujol Health Science Research Institute (IGTP), Barcelona, Spain, emmartinez.germanstrias@gencat.cat