ERC IMMEMO

ERC Advanced Grant Protective and pathogenic immunological memory and its organization by stroma cells (IMMEMO)
The ERC-IMMEMO project (2011 – 2016) aimed to investigate the organization and role of immunological memory, both in protective immunity and in immune-mediated diseases on the molecular and cellular level.
Immunological memory protects us against recurrent infections, but it can also cause damaging immune responses. In chronic immune-mediated diseases, pathogenic immunological memory is likely to be a key driver of inflammation. Some of this inflammation does not respond to either the body’s own regulation, or to standard immunosuppression therapy. Chronic inflammation is therefore a particular challenge for the development of new curative therapeutic strategies.
In IMMEMO, we have developed important new concepts for the organization of immunological memory by stromal cells, as well as for the definition of resting versus active pathogenic memory.

The most relevant results are:
• The long-lasting T-cell memory against systemic pathogens is maintained by memory cells, which are resting in terms of division, cell migration and protein production.

• Long-lived CD8+ memory T cells remain as resting cells in the bone marrow. IL-7 produced by mesenchymal stromal cells is essential for this.

• A protocol for unbiased transcriptome analysis of ex vivo isolated cells was developed.

• The transcription factor Twist1 promotes the survival of pro-inflammatory T-helper cells of type 1 (Th1 cells) in chronically inflamed tissue. Twist1 regulates the microRNA miR-148a, which switches off the pro-apoptotic factor Bim.

• The survival niche of memory plasma cells in the bone marrow consists of stromal cells that create a stable niche by secretion of CXCL-12. APRIL-producing eosinophils, which are subject to a constant renewal process, also contribute to the organisation of this stable niche.

• A method for the targeted depletion of plasma cells according to the specificity of the (auto) antibodies they secrete was developed.

• Protocols for ex vivo analysis of the cytokine production of T-cells were optimized.

We are convinced that our findings can make a decisive contribution to the development of new therapeutic strategies for immune-mediated diseases such as rheumatic and gastrointestinal inflammation, multiple sclerosis, transplant rejection or allergies.
The output of IMMEMO is a total of 30 publications and one patent. 5 PhD theses were completed.