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.

Montico, G., Mingozzi, F., Casciano, F., Protti, G., Gornati, L., Marzola, E., et al. (2023). CCR4+CD8+ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis. EUROPEAN JOURNAL OF IMMUNOLOGY, 53(4 (April 2023)) [10.1002/eji.202149702].

CCR4+CD8+ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis

Mingozzi F.;Protti G.;Gornati L.;Granucci F.;Reali E.
Ultimo
2023

Abstract

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.
Articolo in rivista - Articolo scientifico
Chemokine receptors; Clonal expansion; Psoriasis and psoriatic arthritis; Self-reactive CD8 T cells; T-cell recirculation;
English
1-feb-2023
2023
53
4 (April 2023)
2149702
none
Montico, G., Mingozzi, F., Casciano, F., Protti, G., Gornati, L., Marzola, E., et al. (2023). CCR4+CD8+ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis. EUROPEAN JOURNAL OF IMMUNOLOGY, 53(4 (April 2023)) [10.1002/eji.202149702].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/405041
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