Plasmacytoid predendritic cells initiate psoriasis through interferon-α production

2005/07/04 by Frank O. Nestlé, Frank O. Nestle, Curdin Conrad +8 · 31 citations
Immunology and Microbiology · #T-cell and B-cell Immunology #Psoriasis: Treatment and Pathogenesis #Immunotherapy and Immune Responses

paper · pdf · doi:10.1084/jem.20050500

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)-alpha-producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-alpha early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-alpha signaling or inhibiting the ability of PDCs to produce IFN-alpha prevented the T cell-dependent development of psoriasis. Furthermore, IFN-alpha reconstitution experiments demonstrated that PDC-derived IFN-alpha 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-alpha represent potential early targets for the treatment of psoriasis.

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• Los significados del Caso Pinochet
• Psoriasis
• Dendritic cells and cytokines in human inflammatory and autoimmune diseases. [europepmc]
• Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. [europepmc]
• Resident and "inflammatory" dendritic cells in human skin. [europepmc]
• Mechanisms and consequences of dendritic cell migration. [europepmc]
• Skin-resident T cells: the ups and downs of on site immunity. [europepmc]
• Skin immune sentinels in health and disease. [europepmc]
• Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance. [europepmc]
• Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. [europepmc]
• Plasmacytoid dendritic cells: recent progress and open questions. [europepmc]
• Identification of a novel proinflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis. [europepmc]
• Immunomodulatory functions of type I interferons. [europepmc]
• The role of dendritic cells in autoimmunity. [europepmc]
• Cytokines in psoriasis. [europepmc]
• The multifaceted biology of plasmacytoid dendritic cells. [europepmc]
• Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a. [europepmc]
• Psoriasis pathogenesis and the development of novel targeted immune therapies. [europepmc]
• TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis. [europepmc]
• mRNA vaccines - a new era in vaccinology. [europepmc]
• Emerging Functions of Regulatory T Cells in Tissue Homeostasis. [europepmc]
• The Interplay Between Keratinocytes and Immune Cells in the Pathogenesis of Psoriasis. [europepmc]
• Psoriasis Pathogenesis and Treatment. [europepmc]
• The Dynamics of the Skin's Immune System. [europepmc]
• The Role of Epigenetics in Autoimmune/Inflammatory Disease. [europepmc]
• Keratin 6, 16 and 17-Critical Barrier Alarmin Molecules in Skin Wounds and Psoriasis. [europepmc]
• Signaling pathways and targeted therapies for psoriasis. [europepmc]

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