Psoriasis is a common T cell-mediated autoimmune disease affecting 2% of the global population. While the role of the innate immune system in driving the autoimmune T cell cascade is unclear, this study shows that plasmacytoid pre-dendritic cells (PDCs), natural producers of interferon-alpha (IFN-α), infiltrate psoriatic skin and become activated to produce IFN-α early in disease development. In a xenograft model of human psoriasis, blocking IFN-α signaling or inhibiting PDC IFN-α production prevented T cell-dependent psoriasis development. IFN-α reconstitution experiments confirmed that PDC-derived IFN-α is essential for psoriasis development in vivo. These findings reveal a novel innate immune pathway for triggering psoriasis and suggest that PDCs and their IFN-α are potential targets for psoriasis treatment. PDCs accumulate in psoriatic skin and become activated, leading to IFN-α production, which drives the activation and expansion of pathogenic T cells. Blocking IFN-α signaling inhibited psoriasis development, confirming its role in the disease. PDC-derived IFN-α is necessary and sufficient to drive psoriasis development. The study highlights the importance of PDCs and IFN-α in the pathogenesis of psoriasis, offering new therapeutic targets for treatment.Psoriasis is a common T cell-mediated autoimmune disease affecting 2% of the global population. While the role of the innate immune system in driving the autoimmune T cell cascade is unclear, this study shows that plasmacytoid pre-dendritic cells (PDCs), natural producers of interferon-alpha (IFN-α), infiltrate psoriatic skin and become activated to produce IFN-α early in disease development. In a xenograft model of human psoriasis, blocking IFN-α signaling or inhibiting PDC IFN-α production prevented T cell-dependent psoriasis development. IFN-α reconstitution experiments confirmed that PDC-derived IFN-α is essential for psoriasis development in vivo. These findings reveal a novel innate immune pathway for triggering psoriasis and suggest that PDCs and their IFN-α are potential targets for psoriasis treatment. PDCs accumulate in psoriatic skin and become activated, leading to IFN-α production, which drives the activation and expansion of pathogenic T cells. Blocking IFN-α signaling inhibited psoriasis development, confirming its role in the disease. PDC-derived IFN-α is necessary and sufficient to drive psoriasis development. The study highlights the importance of PDCs and IFN-α in the pathogenesis of psoriasis, offering new therapeutic targets for treatment.