Regulation of nuclear processes by mast cell tryptase - molecular mechanisms and disease implications

Mast cells (MCs) are versatile immune cells mostly known for their detrimental actions in allergic disease, but they have also been implicated in a range of other pathological settings, including cancer, metabolic disease and various skin disorders.

However, the mechanisms by which MCs contribute in such settings are largely unknown, and this lack of knowledge is hampering initiatives to design therapeutic regimes that can target MCs.

A hallmark feature of MCs is their high content of secretory granules filled with various bioactive compounds, including remarkably large amounts of MC-restricted proteases: tryptase, chymase, CPA3. These proteases are released when MCs are activated and can impact on events occurring in the extracellular milieu.

However, we have recently made the striking discovery that one of these proteases - tryptase, also can be found in the nucleus of cells (both in MCs and in target cells), and that tryptase can exert profound effects on nuclear processes.

In this project we will pursue these findings with the Aim to elucidate the molecular mechanisms by which tryptase regulates nuclear processes, and how this affects cellular function.

We believe that this project will contribute to the field of immunology by uncovering fundamentally novel aspects of MC function. Ultimately, this can lead to the design of novel therapeutic strategies where MCs and their products are exploited.