Plasmacytoid predendritic cells initiate psoriasis through interferon-α production

TLDR

Psoriasis is a common T cell–mediated autoimmune disease, and the contribution of the innate immune system to its initiation remains unclear. We found that plasmacytoid dendritic cells infiltrate psoriatic skin, produce interferon‑α early, and that IFN‑α is essential for T‑cell–dependent psoriasis development, highlighting PDCs and IFN‑α as potential early therapeutic targets.

Abstract

Psoriasis is one of the most common T cell–mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-α–producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-α early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-α signaling or inhibiting the ability of PDCs to produce IFN-α prevented the T cell–dependent development of psoriasis. Furthermore, IFN-α reconstitution experiments demonstrated that PDC-derived IFN-α is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-α represent potential early targets for the treatment of psoriasis.