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

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⁺ T_CM cells in the circulation and further expansion in the synovial fluid. Importantly, there was a clonotype overlap between CCR4⁺ T_CM 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.

Keywords: Chemokine receptors; Clonal expansion; Psoriasis and psoriatic arthritis; Self-reactive CD8 T cells; T-cell recirculation.