Introduction

We aim at understanding the mechanisms underlying the deposition and removal of epigenetic modifications in immune cells, the influence of genetic and environmental determinants, and the acquisition of epigenetic alterations in immune-mediated disease including primary immunodeficiencies, autoimmune and autoinflammatory diseases. We also investigate the impact of the epigenetic regulation of immune cells in the microtumour environment.

Our Research

We started these lines of research more than 10 years ago, by studying the occurrence of DNA methylation alterations in the context of systemic lupus erythematosus (SLE), an archetypical systemic autoimmune disease. Later on, we performed new studies with MZ twins discordant for common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency. More recently, our team also demonstrated the occurrence of DNA methylation alterations in monocytes in representative autoinflammatory syndromes. We have shown that alterations in the DNA methylome of peripheral blood monocytes reflect the disease activity in rheumatoid arthritis mediated by the elevated levels of inflammatory cytokines present in such state.

Our Goals

Our main lines of research and specific goals are: 

1. To understand the role of epigenetic control and its upstream determinants in relation with immune function. We aim at understanding how immune cell-cell crosstalk, cytokines and other factors, cell signalling pathways and transcription factors determine epigenetic control and impact immune cell function.

2. To identify epigenetic alterations in immune-mediated diseases and investigate their clinical relevance. Our studies focus on different diseases including primary immunodeficiencies, such as common variable immunodeficiency (CVID) and hyper IgM type 2 syndrome, and autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus.

3. To investigate the effects of immunomodulators and epigenetic compounds in shaping the epigenome and responses of immune cells. We dissect the molecular consequences of different immunomodulators as well as inhibitors of epigenetic enzymes in immune cells.

Our Challenges

The study of epigenetic dysregulation can help understand the determinants of immune dysregulation and can have an impact in the treatment of these diseases. Therefore, with our research we want to answer:

1. How do immune cells translate the surrounding information provided by the direct contact with other cells or the cytokines and other molecules into epigenetic profiles that determine their responses?

2. What is the relevance of the epigenetic alterations that are found in different immune mediated diseases in relation to the aberrant function of these cells?

3. How can we apply the knowledge on the epigenetic dysregulation in immune-mediated disease to the clinics?