Transfection of Vitamin D3-Induced Tolerogenic Dendritic Cells for the Silencing of Potential Tolerogenic Genes. Identification of CSF1R-CSF1 Signaling as a Glycolytic Regulator
Mansilla Lopez, Maria Jose (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
González-Larreategui, Íñigo (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Figa-Martín, Neus (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Barallat, Jaume (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Fondelli, Federico (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Sellés-Rius, Ares (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
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)
Martínez Cáceres, Eva María (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 strategy to re-establish immune tolerance in autoimmune diseases. Among the different strategies available, the use of vitamin D3 for the generation of tolDC (VitD3-tolDC) has been widely tested because of their immune regulatory properties. To identify molecules and pathways involved in the generation of VitD3-tolDC, we established an easy and fast gene silencing method based on the use of Viromer blue to introduce siRNA into monocytes on day 1 of culture differentiation. The analysis of the effect of CD209 (DC-SIGN) and CD115 (CSF1R) down-modulation on the phenotype and functionality of transfected VitD3-tolDC revealed a partial role of CD115 in their tolerogenicity. Further investigations showed that CSF1R-CSF1 signaling is involved in the induction of cell metabolic reprogramming, triggering glycolysis to produce high amounts of lactate, a novel suppressive mechanism of T cell proliferation, recently found in autologous tolerogenic dendritic cells (ATDCs).
Grants:	European Commission 779316 Instituto de Salud Carlos III PI17/01521 Instituto de Salud Carlos III PI20/01313
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:	Tolerance ; Autoimmunity ; Vitamin D3 ; Tolerogenic dendritic cells ; CSF1R ; DC-SIGN
Published in:	International journal of molecular sciences, Vol. 22, Num. 14 (July 2021) , art. 7363, ISSN 1422-0067

DOI: 10.3390/ijms22147363
PMID: 34298983

18 p, 2.5 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