Open Research Projects, Research

Maintenance of immune homeostasis by tissue resident macrophages and microglia in SLE

Prinicipal Investigator

Scientific interest within the context of the graduate college:

Our research aims to understand the role of tissue-resident cells of the innate immune system in the prevention of chronic inflammatory diseases such as systemic lupus erythematosus. Our goal is to identify mechanisms that maintain homeostasis and prevent chronic inflammation and to determine the role of tissue-resident cells of the innate immune system in this process. Understanding such mechanisms may allow to answer the question of why some patients are susceptible to chronic autoimmune-related inflammatory diseases and others are not, and how to improve/achieve resistance to chronic inflammatory diseases.

Project description:

Introduction: Loss of tolerance to nucleic acids and elevated levels of type I interferons (IFN) are linked to autoimmune diseases; however, the basic mechanisms regulating autoimmune pathology are still poorly understood. In systemic lupus erythematosus (SLE) autoantibody production and immune complex deposition are required but not sufficient for organ damage. Tissue-specific cellular regulators that maintain homeostasis and prevent auto-inflammatory responses remain elusive. We have recently found that crosstalk one the one side between innate lymphoid cells and macrophages, and on the other side between macrophages with parenchymal cells may be critical for the maintenance of immune homeostasis in lupus animal models. Here, our overall goal is to identify the mechanisms by which such innate crosstalk occurs in the kidney and/or in the brain before the onset of clinically manifest autoimmune disease. Harnessing such pathways may allow us to prevent organ damage in patients that already have autoantibodies.

Our specific aims are:

Aim 1: To explore the role of innate lymphoid cells for the maintenance of homeostatic macrophage functions.

Aim 2: To dissect how apoptotic cell and/or lipid recognition by macrophages regulates tissue homeostasis

Application details