Plasmacytoid predendritic cells initiate psoriasis through interferon-α production

By Frank O. Nestle, C. Conrad, A. Tun-Kyi, B. Homey, M. Gombert, O. Boyman, G. Burg, Yong‐jun Liu, M. Gilliet. Journal of Experimental Medicine, 2005

1,071 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/4c903c5af3db5c33994cd336881557fc43244767

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In Immunology

1. Yong‐jun Liu
2. M. Gilliet
3. R. Kastelein
4. Frank O. Nestle
5. B. Reizis
6. T. Mcclanahan
7. W. Cao
8. P. Di Meglio

Citations in the corpus

• IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis (2006, background): “Plasmacytoid pre–dendritic cells initiate psoriasis in a xenograft animal model (4), and other cells, including dermal dendritic cells and NK T cells, have also been implicated (5, 6).”
• Plasmacytoid Dendritic Cells: Recent Progress and Open Questions (2011, background): “In psoriasis, early skin lesions are highly infiltrated by activated pDCs, corresponding with decreased numbers of circulating pDCs in the blood (134).”
• Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 (2009, background): “Psoriasis is characterized by an early skin infiltration of pDC and their aberrant activation to produce IFN- (Nestle et al., 2005).”
• Type I interferon in systemic lupus erythematosus and other autoimmune diseases. (2006, neutral): “In a xenograft model of human psoriasis, blocking IFN-a signaling or inhibiting the ability of pDCs to produce IFN-ab prevented the T cell-dependent disease development (Nestle et al., 2005).”
• Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases (2008, background): “The resulting activation of pDCs triggers autoreactive T-cell activation and initiates the development of skin lesions through type I IFN”
• Skin immune sentinels in health and disease (2009, background): “pDCs are rare in healthy skin but have been implicated in the pathogenesis of systemic lupus erythematosus and psoriasi”