Simon Brunel, Ph.D.

Can we cure autoimmune diseases with a single therapy?

Autoimmune diseases such as psoriasis, scleroderma, multiple sclerosis, diabetes or immune disorders such as allergies are due to a misguided or disproportionate immune reaction. Autoimmune disorders are sharply on the rise in modern society particularly affecting women. Available treatments consist of daily or emergency medications. Therefore, I propose a novel approach that re-edits the immune cells involved in the autoimmune reaction, targeting autoimmune diseases at their root.

The main culprit in most autoimmune disease are autoreactive T cells, which recognize and destroy cells in the body. T cells are generated and educated in the thymus, a small organ in front of the heart, before they travel throughout the body. Our goal is to prevent autoreactive T cells from leaving the thymus.

Recently, it has been shown that a subset of immune cells, so called plasmacytoid dendritic cells (pDCs), are able, under certain conditions, to migrate to the thymus and trigger the death of the autoreactive T cells. They are doing so by capturing and displaying fragments of tissue proteins on their surface. When these “loaded” dendritic cells travel to the thymus and they trigger the self-destruction of any immune cells that recognize that particular tissue protein, thus eliminating autoreactive T cells.

The purpose of this project is to mimic this physiological elimination process by generating pDC that express tissue proteins and can find their way to the thymus in a mouse model of type 1 diabetes. In mice just as in humans with type 1 diabetes, autoreactive T cells recognize insulin and destroy the cells that produce it. In healthy people, trace amounts of insulin are present in the thymus helping to build a natural immune tolerance of insulin. I will inject modified pDCs that carry insulin into the thymus of NOD mice, which spontaneously develop type 1 diabetes, to build this immune tolerance and prevent the development of diabetes.

SPARKing Impact: If this novel therapeutic strategy works, it could represent a universal therapeutic approach for any autoimmune diseases.