Bruno Kyewski

The thymus, a lymphoid organ located above the heart, is the site where the immune system learns how to discriminate between self and non-self. Immune cells are selected based upon their ability to react against foreign pathogens and at the same time tolerate the body’s own cells and tissues. How this process works has been investigated in great detail in recent years.

One peculiarity of the thymus is its early degeneration or involution starting around puberty. In fact, it is the first organ in the body to show this age-related decline. At the same time, it is well known that the incidence of autoimmune diseases increases with age. Not surprisingly, a link between these two observations has been repeatedly construed without offering a clear mechanistic explanation in which way thymic involution would affect the thymic tolerance process. In this project we will address this question with a new twist by focussing on the phenomenon of promiscuous gene expression (pGE), where genes expressed only in other parts of the body, or only by the opposite sex, are also expressed in the thymus by medullary thymic epithelial cells (mTECs). Promiscuous gene expression has been shown to be essential to prevent organ-specific autoimmunity.