Ricerca Progetti nazionali, regionali, internazionaliNAZIONALIPRIN 2022Characterizing the role of CD300e

Characterizing the role of CD300e receptor in obesity: low-grade inflammation, insulin-resistance and immunomodulatory properties

Adipose tissue (AT) is a critical regulator of systemic metabolism. The hallmark of AT dysregulation in obesity is the appearance of a low-grade inflammation, characterized by increased infiltration and activation of innate and adaptive immune cells. The low-grade inflammation along with the appearance of insulin resistance is the prerequisite for the progression from obesity toward type 2 diabetes (T2D). CD300e is an immune receptor expressed on immune and non-immune cells including adipocytes. Its activation hampers the insulin-induced phosphorylation of Akt and upregulates the expression of B7.2/CD86. T2D patients and obese patients (OP) are seropositive for CD300e and our preliminary data showed that CD300e is upregulated in subcutaneous fat (SAT) of OP, while it drops after weight loss. The aim of the present project is to correlate the expression of the immune receptor by adipose tissue macrophages, and their pro-inflammatory profile, with the dysmetabolic state, namely T2D, and to characterize the molecular pathways at the interface between immune system (both innate and adaptive) and adipocytes. The project will be performed by three highly integrated Research Units (RUs) with complementary expertise aiming to:

1. Define the contribution of CD300e to the low-grade inflammation in obese patients with or without T2D

2. Confirm the role of CD300e receptor expressed by myeloid cells to the low-grade inflammation and insulin-resistance in vivo

3. Dissect the CD300e-dependent molecular pathways at the interface between adipocytes and immune system, with a focus on the adaptive immunity

4. Demonstrate the predictive significance of the anti-CD300e antibodies titer in improving insulin sensitivity in OP, after weight loss.

The research project will elucidate important questions on the immunopathogenesis of AT dysfunctions and will exploit CD300e as a new disease-associated biomarker whose validation could facilitate the development of novel therapeutic strategies for the treatment of both obesity and atherosclerosis.

 

Data di avvio 28 Settembre 2023

Data di completamento 28 Settembre 2025

Total cost  € 18498,00

 

Progetto 2022YXZ2RB finanziato all’interno del Bando PRIN 2022 di cui al Decreto Direttoriale n. 104 del 02/02/2022 nell’ambito del Piano Nazionale di Ripresa e Resilienza, Missione 4 – Componente 2. Dalla Ricerca all’Impresa - Investimento 1.1 Fondo per il Programma Nazionale della Ricerca (PNR) e Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN), finanziato dall’Unione europea – NextGenerationEU – CUP B53D23003720006