Molecular control of tolerogenic dendritic cell function

New York University School Of Medicine, New York NY

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT Dendritic cells (DCs) are the key sentinel cells of the immune system that directly recognize pathogens and initiate adaptive T and B cell responses. In addition to their essential role in antimicrobial and antitumor immunity, DCs are thought to control immune homeostasis and promote tolerance. Conversely, aberrant antigen presentation and/or cytokine production by DCs have been implicated in nearly every autoimmune disease. However, the role and mechanism of the tolerogenic function of DCs are poorly understood. In particular, the control of the "switch" between the tolerogenic and immunogenic DC function and the molecular programs underlying these functions remain largely unknown. Our preliminary studies have identified a potential molecular regulator of tolerogenic DCs, whose deletion impairs DC function and leads to the loss of T cell tolerance. The proposed project will seek to pinpoint the DC subset responsible for this phenotype (Aim 1) and characterize its molecular basis, including aberrant cytokine production (Aim 2) and impaired signaling (Aim 3). Collectively, these studies would help delineate the molecular control of tolerogenic DCs and provide insights into the mechanisms of DC-mediated peripheral tolerance.