Regulation and function of alternatively activated macrophage markers; a focus on E-cadherin.

Macrophages are innate immune cells which coordinate adaptive immune responses and are crucial mediators of inflammation. Classicaly activated macrophages (CAMs or M1), induced by Th1 cytokines (IFN-gamma) and Toll-like receptor ligands (LPS), are pro-inflammatory and play a fundamental role in pathogen clearane. Yet, uncontrolled inflammation can induce collateral tissue damage and must be repressed once the microbial threat is eliminated. To do so, macrophages are instructed by diverse anti-inflammatory factors, including the Th2 cytokines IL-4 and IL-13 (inducing alternatively activated macrophages (AAMs)), IL-10, TGF-beta, glucocorticoids, and immune complexes. All these types of anti-inflammatory macrophages are often grouped under the generic term M2. Functionally, M2 macrophages dampen type I inflammatory responses, promote angiogenesis and wound healing an are implicated in Th2 cytokine-driven diseases such as asthma and helminth infections. Nevertheless, the molecular mediators accounting for these functions remaind poorly characterized and markers which discriminate between AAMs and other M2 remained scarce. Before the start of this PhD, our laboratory published a collection of signature genes overexpressed in M2 compared with M1 cells. This publication was the first to report E-cadherin (Cdh1) as a potential marker for the M2 activation status. At that moment, the cell/cell adhesion molecule E-cadherin had only been studies in detail in epithelial cells and to some point in Langerhans cells. The main goal of this PhD was to investigate the regulation and function of E-cadherin in macrophages.