Inflammation is established as a causal factor in developing type-2 diabetes (T2D). We reported that inflammation in T2D arises through the transcription factor Interferon regulatory factor (Irf)-5 in adipose tissue and liver macrophages (Dalmas et al 2015; Alzaid et al 2016). Here, I present preliminary data placing Irf5 as a central mediator of bioenergetic adaptation, repressing mitochondrial respiration to optimise inflammatory polarisation. Accordingly, I aim to interrogate Irf5-dependent mediators of cellular metabolism as sensors of inflammation and novel therapeutic targets. Over three work packages, I first characterise immunogenicity of metabolic signals. Next, in vitro and in vivo screening decipher Irf5-dependent bioenergetic pathways for preclinical evaluation. Lastly, a fully translational work package is dedicated to in vivo therapeutic proof-of-principle studies and evaluating Irf5-mediated inflammation as a predictive biomarker of diabetogenesis.
Monsieur Fawaz ALZAID (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
INSERM - U 1151 INEM INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
U1138 Cordeliers CENTRE DE RECHERCHE DES CORDELIERS
Help of the ANR 304,397 euros
Beginning and duration of the scientific project: December 2019 - 48 Months