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

Fabio Casciano¹Paolo Severi²Laura Marongiu³Anna Caproni¹Chiara Terranova¹Alex Spitilli¹Davide Ferrari¹Chiara Ruzza¹Peggy Marconi¹Paola Rizzo¹Francesca Granucci³Paola Secchiero¹Eva Reali^1,2*

• ¹University of Ferrara, Ferrara, Emilia-Romagna, Italy
• ²Department of Translational Medicine, University of Ferrara, Ferrara, Italy
• ³University of Milano-Bicocca, Milan, Lombardy, Italy

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 cells 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 + cells as well as CD8 + T cells with a highly differentiated phenotype.Notably, parallel analysis in aorta samples revealed upregulation of endothelial dysfunction (Icam1, Vcam1) and vascular inflammation markers (Ccl2, Olr1), together with a trend towards increased expression of the CXCR3 ligand, Cxcl10. 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.