Antoine Caillon, Lady Davis Institute
Supervisor: Ernesto Schiffrin, Lady Davis Institute
T cells* play a predominant role during induction and peak of the inflammatory response in autoimmune and chronic inflammatory diseases like rheumatoid arthritis or lupus. Classically, T cells are activated after recognition of foreign or transformed molecules. This activation is mediated by their T-Cell Receptor or TCR. Recently, different research groups including our laboratory had described roles of T cell populations during hypertension, characterized by an increase of blood pressure, and blood vessel damage. These effects were generated by pro-inflammatory molecules releasing by T cells, mimicking some pro-inflammatory chronic diseases. Focusing on T cell population, two populations can be separated based on the expression of the TCR, α/β TCR T cells representing the majority of the T-cells (96-99%) and a very small population, γ/δ TCR T cells representing 1 to 4 % of the T-cells. It has been shown that γ/δ T cells could play a role in the initiation of inflammatory response and to produce a pro-inflammatory molecule, interleukin-17A (IL-17A), when activated. However, whether this T cells subset plays a role in the development of hypertension and associated blood vessel injury is still unknown. The role of γ/δ T cells in hypertension will be investigated in an animal model of hypertension using normal mice and mice deficient in γ/δ T cells, α/β T cells or all T cells. In addition, the γ/δ T cells will be investigated in the blood and gluteal subcutaneous biopsies of normotensive subjects and human patients with essential hypertension and hypertension with complications such as type 2 diabetes and chronic kidney disease. Ours preliminary results show that in absence of γ/δ T cells, all the hypertension events like increase of blood pressure and artery injury, were blunting, and preliminary observation in human hypertension seems to show a positive correlation between γ/δ T cells producing IL-17a and blood pressure. These very promising results will permit to understand the role of the initiation of inflammation in hypertension and open hopes in for the development of new treatments in hypertension. Our study on γ/δ T cells is very well included in the current priority of research areas sustain by Canadian vascular network because this research project reveals a key cell population mediating the pathology and because γ/δ T cells could be at the same time a new biomarker and a molecular target for hypertension therapy.
*T cells: orchestra conductors of the immune process, drive a pro- or anti-inflammation and coordinate its intensity during inflammation (short lay summary).