Vitamin D3-Induced Tolerogenic Dendritic Cells Modulate the Transcriptomic Profile of T CD4 + Cells Towards a Functional Hyporesponsiveness
Navarro-Barriuso, Juan (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Mansilla Lopez, Maria Jose (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Quirant, Bibiana (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Teniente Serra, Aina (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Ramo-Tello, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martínez-Cáceres, Eva M. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Date:	2021
Abstract:	The use of autologous tolerogenic dendritic cells (tolDC) has become a promising alternative for the treatment of autoimmune diseases. Among the different strategies available, the use of vitamin D3 for the generation of tolDC (vitD3-tolDC) constitutes one of the most robust approaches due to their immune regulatory properties, which are currently being tested in clinical trials. However, the mechanisms that vitD3-tolDC trigger for the induction of tolerance remain elusive. For this reason, we performed a full phenotypical, functional, and transcriptomic characterization of T cells upon their interaction with autologous, antigen-specific vitD3-tolDC. We observed a strong antigen-specific reduction of T cell proliferation, combined with a decrease in the relative prevalence of T1 subpopulations and IFN- γ production. The analysis of the transcriptomic profile of T CD4 + cells evidenced a significant down-modulation of genes involved in cell cycle and cell response to mainly pro-inflammatory immune-related stimuli, highlighting the role of JUNB gene as a potential biomarker of these processes. Consequently, our results show the induction of a strong antigen-specific hyporesponsiveness combined with a reduction on the T1 immune profile of T cells upon their interaction with vitD3-tolDC, which manifests the regulatory properties of these cells and, therefore, their therapeutic potential in the clinic. https://doi. org/10. 13039/5011000033295https://doi. org/10. 13039/5011000033293https://doi. org/10. 13039/5011000033296https://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329_https://doi. org/10. 13039/501100003329_https://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Tolerogenic dendritic cells ; Immune tolerance ; T cells ; Antigen-specific response ; Transcriptomic study
Published in:	Frontiers in immunology, Vol. 11 (january 2021) , ISSN 1664-3224

DOI: 10.3389/fimmu.2020.599623
PMID: 33552054

14 p, 1.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles