Research project

Unveiling the multifaceted activities of BG12 (dimethylfumarate) on immune tolerance through its action on the systemic immunometabolic asset and regulatory T cell functions (DSB.AD001.073)

Thematic area

Biomedical sciences

Project area

Oncologia e Immunologia (DSB.AD001)

Structure responsible for the research project

Institute Experimental Endocrinology and Oncology "Gaetano Salvatore" (IEOS)

Project manager

GIUSEPPE MATARESE
Phone number: 0817464580
Email: giuseppe.matarese@cnr.it

Abstract

Capitalizing our long standing experience in immunity and metabolism we will investigate at cellular and molecular level the effect of DMF on the main metabolic pathways characterizing T cells, with particular emphasis towards Treg and Tconv cells in both human and mouse systems. This specific study should allow to understand whether the effects of DMF, besides its known activities on the classical anti-inflammatory and neuroprotective side in multiple sclerosis (MS), should be related to its capacity to switch T cell biology from specific metabolic pathways induced during autoimmunity (ie. glycolysis) towards pro-tolerizing metabolic pathways (ie. lipid oxidation). This novel approach should help to understand the molecular mechanism of action of DMF, on one side, and to find novel immunometabolic markers to monitor MS disease progression and possible side effects during DMF treatment.

Goals

1) Valutare la capacità del DMF (BG12) di alterare l'equilibrio tra metabolismo glicolitico/lipidico, che è noto essere in grado di controllare l'attivazione delle cellule immunitarie.
2) Identificare la relazione tra stato metabolico, DMF e cellule Treg nel contesto di malattie autoimmunitarie
3) Dissezionare il microambiente necessario per la genesi delle Treg ed il ruolo del DMF in questo processo
4) Definire le basi cellulari e molecolari per l'uso del DMF per modulare la risposta delle cellule T in patologie autoimmunitarie come la sclerosi multipla
5) Investigare la possibilità di espandere le cellule Treg con DMF come nuovo approccio terapeutico per la SM.

Start date of activity

18/11/2015

Keywords

Treg cells, metabolism, DMF

Last update: 28/03/2024