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

Psoriasis is a chronic inflammatory skin disease with an autoimmune component and is associated with joint inflammation. 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. We evaluated the expansion of OT-I OVA-specific 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 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 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 circulating CCR4 + T CM 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. Skin-primed self-reactive T cells egressing to the blood cloud localize and clonally expand at distant organs. This mechanism could represent a link between skin and joint manifestations in psoriasis patients at risk of developing psoriatic arthritis. This article is protected by copyright. All rights reserved.