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...

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Main Authors: Fabio Casciano, Paolo Severi, Laura Marongiu, Anna Caproni, Chiara Terranova, Alex Spitilli, Davide Ferrari, Chiara Ruzza, Peggy Marconi, Paola Rizzo, Francesca Granucci, Paola Secchiero, Eva Reali
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1574455/full
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author Fabio Casciano
Paolo Severi
Laura Marongiu
Anna Caproni
Chiara Terranova
Alex Spitilli
Davide Ferrari
Chiara Ruzza
Peggy Marconi
Paola Rizzo
Paola Rizzo
Francesca Granucci
Paola Secchiero
Eva Reali
author_facet Fabio Casciano
Paolo Severi
Laura Marongiu
Anna Caproni
Chiara Terranova
Alex Spitilli
Davide Ferrari
Chiara Ruzza
Peggy Marconi
Paola Rizzo
Paola Rizzo
Francesca Granucci
Paola Secchiero
Eva Reali
author_sort Fabio Casciano
collection DOAJ
description 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 (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.
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spelling doaj-art-ada951b6a6fb4f52b76877e729c8adc62025-08-20T02:07:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15744551574455Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasisFabio Casciano0Paolo Severi1Laura Marongiu2Anna Caproni3Chiara Terranova4Alex Spitilli5Davide Ferrari6Chiara Ruzza7Peggy Marconi8Paola Rizzo9Paola Rizzo10Francesca Granucci11Paola Secchiero12Eva Reali13Department of Environmental and Prevention Sciences and LTTA Centre, University of Ferrara, Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, Ferrara, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, ItalyDepartment of Environmental and Prevention Sciences and LTTA Centre, University of Ferrara, Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, Ferrara, ItalyDepartment of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyDepartment of Neurosciences and Rehabilitation, University of Ferrara, Ferrara, ItalyDepartment of Environmental and Prevention Sciences and LTTA Centre, University of Ferrara, Ferrara, ItalyDepartment of Translational Medicine and LTTA Centre, University of Ferrara, Ferrara, ItalyMaria Cecilia Hospital, GVM Care & Research, Cotignola, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, ItalyDepartment of Translational Medicine, University of Ferrara, Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, Ferrara, ItalyPsoriasis 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 (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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1574455/fullT cellsmouse model of recurrent psoriasisendothelial dysfunctionvascular inflammationcardiovascular comorbidities
spellingShingle Fabio Casciano
Paolo Severi
Laura Marongiu
Anna Caproni
Chiara Terranova
Alex Spitilli
Davide Ferrari
Chiara Ruzza
Peggy Marconi
Paola Rizzo
Paola Rizzo
Francesca Granucci
Paola Secchiero
Eva Reali
Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis
Frontiers in Immunology
T cells
mouse model of recurrent psoriasis
endothelial dysfunction
vascular inflammation
cardiovascular comorbidities
title Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis
title_full Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis
title_fullStr Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis
title_full_unstemmed Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis
title_short Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis
title_sort highly differentiated t cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis
topic T cells
mouse model of recurrent psoriasis
endothelial dysfunction
vascular inflammation
cardiovascular comorbidities
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1574455/full
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