Prof. Orly Avni

Regulation of gene expression in the immune system in health and disease

The immune system distinguishes between self and non-self but also between different types of non-self such as viruses and worms. T helper (Th) cells (CD4+) have a fundamental role in that challenge; following their first interaction with a pathogen, Th cells can differentiate into regulatory or effector lineages that differentially express cytokine genes. The effector lineages Th1, Th2, and Th17 are characterized by the expression of the signature cytokines Interferon g (IFNg), Interleukin-4 (IL-4), and Interleukin-17 (IL-17), respectively. IFNg exerts protective functions in microbial infections and is observed clinically in cases of autoimmune diseases. IL-4 is strongly apparent in parasitic infections, and is associated with allergic reactions. IL-17 plays a role in eradication of extracellular pathogens, but inappropriate responses can lead to autoimmunity

Following differentiation, Th cells may enter a resting state, in which they do not express cytokines; nonetheless, they ‘remember’ their transcriptional program and express the appropriate set of cytokines in response to subsequent antigen stimulation. However, this process is more flexible than previously appreciated and under specific circumstances, Th cells can gain the expression of the opposing cytokines or even re-differentiate toward other Th lineages. This plasticity probably assists the immune system to cope with new immunological challenges

Since immunological diseases such as autoimmunity and allergy are associated with aberrant expression of cytokines in Th cells, elucidation of the epigenetic regulation of these genes can facilitate the development of novel therapies. We study the epigenetic regulation of differentiated murine and human Th cells, especially as regard to the function of the polycomb group proteins.  Disregulation of the immune function is associated with many other human diseases, and we are also interested in some aspects of the connections between the immune system and the brain