Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis

Psoriasis is a chronic inflammatory skin-disease associated with cardiovascular comorbidities. In patients, T cells with a skin-primed phenotype are expanded in peripheral blood, indicating a role for skin to blood T cell recirculation in the development of systemic comorbidities. Here, we aimed to investigate (i) the establishment of CD4⁺ and CD8⁺ T cell memory, (ii) the accumulation of activated and terminally differentiated T cells, and (iii) the potential link with vascular inflammation, in a mouse model of recurrent psoriasis. The results revealed systemic accumulation of memory T cells in the mouse model and similar results in patients with psoriatic disease. Recurrent psoriasis-like condition in mice also induced increased activation of memory T cells, augmented frequencies of CXCR3⁺4-1BB⁺ and PD-1⁺TIM-3⁺ CD4⁺ T cells as well as CD8⁺ T cells with a highly differentiated phenotype. Notably, parallel analysis in aorta samples revealed upregulation of endothelial dysfunction (<i>Icam1, Vcam1</i>) and vascular inflammation markers (<i>Ccl2, Olr1</i>), together with a trend towards increased expression of the CXCR3 ligand, <i>Cxcl10</i>. Importantly CXCR3⁺LFA-1⁺ CD4⁺ and CD8⁺ T cell effectors were markedly enhanced at systemic level, thus providing insights into the mechanistic link between highly differentiated T cells, endothelial dysfunction and vascular inflammation.