| Autor: |
Montico, Guendalina, Mingozzi, Francesca, Casciano, Fabio, Protti, Giulia, Gornati, Laura, Marzola, Erika, Banfi, Giuseppe, Guerrini, Remo, Secchiero, Paola, Volinia, Stefano, Granucci, Francesca, Reali, Eva |
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| Zdroj: |
European Journal of Immunology; Apr2023, Vol. 53 Issue 4, p1-13, 13p |
| Abstrakt: |
Psoriasis is a chronic inflammatory skin disease with an autoimmune component and associated with joint inflammation in up to 30% of cases. To investigate autoreactive T cells, we developed an imiquimod‐induced psoriasis‐like inflammation model in K5‐mOVA.tg C57BL/6 mice expressing ovalbumin (OVA) on the keratinocyte membrane, adoptively transferred with OT‐I OVA‐specific CD8+ T cells. We evaluated the expansion of OT‐I CD8+ T cells and their localization in skin, blood, and spleen. scRNA‐seq and TCR sequencing data from patients with psoriatic arthritis were also analyzed. In the imiquimod‐treated K5‐mOVA.tg mouse model, OT‐I T cells were markedly expanded in the skin and blood at early time points. OT‐I T cells in the skin showed mainly CXCR3+ effector memory phenotype, whereas in peripheral blood there was an expansion of CCR4+CXCR3+ OT‐I cells. At a later time point, expanded OVA‐specific T‐cell population was found in the spleen. In patients with psoriatic arthritis, scRNA‐seq and TCR sequencing data showed clonal expansion of CCR4+ TCM cells in the circulation and further expansion in the synovial fluid. Importantly, there was a clonotype overlap between CCR4+ TCM in the peripheral blood and CD8+ T‐cell effectors in the synovial fluid. This mechanism could play a role in the generation and spreading of autoreactive T cells to the synovioentheseal tissues in psoriasis patients at risk of developing psoriatic arthritis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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