Ricerc@Sapienza

Oxysterols, oxidized derivatives of cholesterol found in LDL and atherosclerotic plaques, trigger several biological responses involved in the initiation and progression of atherosclerosis. Endothelial dysfunction, which occurs when vascular homeostasis is altered, plays a key role in the pathogenesis of several metabolic diseases. The contribution of endoplasmic reticulum (ER) stress to endothelial disfunction is a relatively recent area of investigation.

Macrophage activation by Toll receptors is an essential event in the development of the response against pathogens. NOTCH signaling pathway is involved in the control of macrophage activation and the inflammatory processes. In this work, we have characterized NOTCH signaling in macrophages activated by Toll-like receptor (TLR) triggering and determined that DLL1 and DLL4 are the main ligands responsible for NOTCH signaling. We have identified ADAM10 as the main protease implicated in NOTCH processing and activation.

The Notch signaling pathway plays multiple roles in driving T-cell fate decisions,
proliferation, and aberrant growth. NF-kB is a cell-context key player interconnected
with Notch signaling either in physiological or in pathological conditions. This review
focuses on how themultilayered crosstalk between different Notches and NF-kB subunits
may converge on Foxp3 gene regulation and orchestrate CD4+ regulatory T (Treg)
cell function, particularly in a tumor microenvironment. Notably, Treg cells may play a