Epigenetic regulation by DAMPs underlying trained immunity in health and disease

Concept

Trained immunity is a process of innate immune memory in which a primary stimulus, such as β-glucan, enhances the response of monocytes upon nonspecific re-stimulation. During trained immunity, an epigenetic reprogramming of monocytes is observed, characterized by histone methylation marks in pro-inflammatory genes and an increased production of TNFa and IL-6. In humans, apart from the protection from re-infection, this process might lead in the long-term to the development and/or persistence of chronic inflammatory conditions. The hypothesis that trained immunity contributes to the initiation and perpetuation of the inflammatory response in rheumatoid arthritis (RA) has not been investigated so far.

Facts and figures

Project lead
K Laskari
Athens University Medical School
katerina_laskari@yahoo.gr
FOREUM research grant: €50'000
Project Duration: 2019–2020

Meet the team

K Laskari
Athens University Medical School
P Sfikakis
Athens University Medical School
Prof. Dr. O Distler
University of Zurich

Objectives

In the current proposal, we aim to better investigate pathogen-associated and damage-associated molecular pattern (PAMP and DAMP, respectively)-induced trained immunity in healthy individuals and RA patients. The association of epigenetic modifications with transcriptomic data will identify gene promoters, enhancers and transcription factor motifs possibly involved in trained immunity. Gene silencing will give more insights into their function. By targeting specific mechanisms of trained immunity on either molecular, protein or epigenetic level, novel therapeutic approaches could be developed.

Patient Voice

For this laboratory project, based on novel technologies, patients have not been directly involved
in the design of the experiments. However, the development of novel potential therapeutic targets and strategies will clearly benefit the patients.

Goals/Milestones

1. The characterization of the innate immune memory process in healthy human monocytes (month 1-4)
2. The investigation of the innate immune memory process in RA (month 4-9)
3. The analysisof trascriptomic and epigenetic changes leading to innate immune memory (month 6-12)