The study evaluates the feasibility and therapeutic efficacy of CD123-targeting CAR-T cells derived from patients with immune-mediated inflammatory diseases, including psoriasis, hidradenitis suppurativa, systemic lupus erythematosus, and systemic sclerosis. In vitro and in vivo experiments investigated their ability to eliminate plasmacytoid dendritic cells and reduce inflammatory skin pathology.
Patient-derived CD123 CAR-T cells efficiently depleted plasmacytoid dendritic cells in vitro and in vivo, with functionality comparable to CAR-T cells from healthy donors. In humanized mice, CAR-T cells migrated to inflamed skin, reduced plasmacytoid dendritic cell infiltration, restored epidermal architecture, and decreased psoriasis-like inflammation.
genO-BRGSF-HIS humanized mouse — genOway-developed, an immunodeficient BRGSF mouse engrafted with human hematopoietic stem cells to establish a functional human immune system. The model was treated with human Flt3 ligand to support human dendritic cell populations and subjected to imiquimod-induced psoriasis-like skin inflammation. It enabled in vivo assessment of human CD123 CAR-T cell activity, plasmacytoid dendritic cell depletion, and therapeutic effects on inflamed skin.
Autoimmunity, immune-mediated inflammatory diseases, psoriasis, hidradenitis suppurativa, systemic lupus erythematosus, systemic sclerosis, CAR-T cell therapy, plasmacytoid dendritic cells, targeted cell depletion, inflammatory skin disease
genO-BRGSF-HIS, humanized immune system mouse, human hematopoietic stem cell engraftment, human immune cell reconstitution, human Flt3 ligand treatment, imiquimod-induced psoriasis model, human CD123 CAR-T cell evaluation, plasmacytoid dendritic cell depletion, in vivo therapeutic efficacy
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