Study of the mechanism that triggers a rare autoimmune disease with onset in infancy

Philippe Pierre

Universidade de Aveiro, Portugal

The body has to constantly adapt to stressful situations caused by environmental or genetic factors. To do this, it has several mechanisms at its disposal that prevent the normal functioning of cells and tissues from being disrupted. One of these is the integrated stress response, a circuit of molecules that responds to stressors by regulating and balancing protein synthesis. This circuit is mediated by the PERK protein, necessary for the production of type I interferon, which helps to regulate the activity of the immune system. Patients prone to autoimmune diseases have been found to have several mutations in the genes that regulate this mechanism.

Similarly, the discovery of mutations in two genes in children who suffer from a rare autoimmune disease called SAVI (STING-associated vasculopathy with onset in infancy), underlines the need to better understand the molecular processes leading to the development of this type of disease.

In this regard, this project will study immune cells with pathogenic interferon production and will use capillary blood vessel organoids to elucidate how the mutations found in patients can amplify vasculopathies. Using a multidisciplinary approach, the researchers will attempt to define the relationship between the integrated stress response circuit and the STING gene, in the context of the onset in infancy of interferonopathies and vasculopathies.

Exploring the PERK/STING axis in Pathological Inflammatory Conditions

€499,931.66