Authors:	Leuenberger, Tina Pfueller, Caspar Lüssi, Felix Bendix, Ivo Paterka, Magdalena Prozorovski, Timour Treue, Denise Luenstedt, Sarah Herz, Josephine Siffrin, Volker Infante-Duarte, Carmen Zipp, Frauke Waicies, Sonia
Title:	Modulation of dendritic cell immunobiology via inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase
Online publication date:	13-Jun-2022
Year of first publication:	2014
Language:	english
Abstract:	The maturation status of dendritic cells determines whether interacting T cells are activated or if they become tolerant. Previously we could induce T cell tolerance by applying a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor (HMGCRI) atorvastatin, which also modulates MHC class II expression and has therapeutic potential in autoimmune disease. Here, we aimed at elucidating the impact of this therapeutic strategy on T cell differentiation as a consequence of alterations in dendritic cell function. We investigated the effect of HMGCRI during differentiation of peripheral human monocytes and murine bone marrow precursors to immature DC in vitro and assessed their phenotype. To examine the stimulatory and tolerogenic capacity of these modulated immature dendritic cells, we measured proliferation and suppressive function of CD4+ T cells after stimulation with the modulated immature dendritic cells. We found that an HMGCRI, atorvastatin, prevents dendrite formation during the generation of immature dendritic cells. The modulated immature dendritic cells had a diminished capacity to take up and present antigen as well as to induce an immune response. Of note, the consequence was an increased capacity to differentiate naïve T cells towards a suppressor phenotype that is less sensitive to proinflammatory stimuli and can effectively inhibit the proliferation of T effector cells in vitro. Thus, manipulation of antigen-presenting cells by HMGCRI contributes to an attenuated immune response as shown by promotion of T cells with suppressive capacities
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7129
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	PLoS one 9 7
Pages or article number:	e100871
Publisher:	PLoS
Publisher place:	Lawrence, Kan.
Issue date:	2014
ISSN:	1932-6203
Publisher URL:	http://dx.doi.org/10.1371/journal.pone.0100871
Publisher DOI:	10.1371/journal.pone.0100871
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)