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Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide

Author

Listed:
  • Roberto Lande

    (and)

  • Josh Gregorio

    (and)

  • Valeria Facchinetti

    (and)

  • Bithi Chatterjee

    (Yale University School of Medicine, New Haven, Connecticut 06520-8002, USA
    Genentech., 1 DNA Way, South San Francisco, California 94080, USA)

  • Yi-Hong Wang

    (and)

  • Bernhard Homey

    (Heinrich-Heine-University, Düsseldorf 40225, Germany)

  • Wei Cao

    (and)

  • Yui-Hsi Wang

    (and)

  • Bing Su

    (and)

  • Frank O. Nestle

    (St John’s Institute of Dermatology, King’s College London School of Medicine)

  • Tomasz Zal

    (and)

  • Ira Mellman

    (Yale University School of Medicine, New Haven, Connecticut 06520-8002, USA
    Genentech., 1 DNA Way, South San Francisco, California 94080, USA)

  • Jens-Michael Schröder

    (University Hospital Schleswig-Holstein, Campus Kiel, University of Kiel)

  • Yong-Jun Liu

    (and)

  • Michel Gilliet

    (and
    M. D. Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA)

Abstract

Plasmacytoid dendritic cells (pDCs) sense viral and microbial DNA through endosomal Toll-like receptors to produce type 1 interferons. pDCs do not normally respond to self-DNA, but this restriction seems to break down in human autoimmune disease by an as yet poorly understood mechanism. Here we identify the antimicrobial peptide LL37 (also known as CAMP) as the key factor that mediates pDC activation in psoriasis, a common autoimmune disease of the skin. LL37 converts inert self-DNA into a potent trigger of interferon production by binding the DNA to form aggregated and condensed structures that are delivered to and retained within early endocytic compartments in pDCs to trigger Toll-like receptor 9. Thus, our data uncover a fundamental role of an endogenous antimicrobial peptide in breaking innate tolerance to self-DNA and suggest that this pathway may drive autoimmunity in psoriasis.

Suggested Citation

  • Roberto Lande & Josh Gregorio & Valeria Facchinetti & Bithi Chatterjee & Yi-Hong Wang & Bernhard Homey & Wei Cao & Yui-Hsi Wang & Bing Su & Frank O. Nestle & Tomasz Zal & Ira Mellman & Jens-Michael Sc, 2007. "Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide," Nature, Nature, vol. 449(7162), pages 564-569, October.
    • Handle: RePEc:nat:nature:v:449:y:2007:i:7162:d:10.1038_nature06116
    DOI: 10.1038/nature06116
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    Cited by:

    1. Antonio Julià & Alba Erra & Carles Palacio & Carlos Tomas & Xavier Sans & Pere Barceló & Sara Marsal, 2009. "An Eight-Gene Blood Expression Profile Predicts the Response to Infliximab in Rheumatoid Arthritis," PLOS ONE, Public Library of Science, vol. 4(10), pages 1-8, October.
    2. Silke M Currie & Emily Gwyer Findlay & Brian J McHugh & Annie Mackellar & Tian Man & Derek Macmillan & Hongwei Wang & Paul M Fitch & Jürgen Schwarze & Donald J Davidson, 2013. "The Human Cathelicidin LL-37 Has Antiviral Activity against Respiratory Syncytial Virus," PLOS ONE, Public Library of Science, vol. 8(8), pages 1-10, August.
    3. Feiyang Ma & Olesya Plazyo & Allison C. Billi & Lam C. Tsoi & Xianying Xing & Rachael Wasikowski & Mehrnaz Gharaee-Kermani & Grace Hile & Yanyun Jiang & Paul W. Harms & Enze Xing & Joseph Kirma & Jing, 2023. "Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Hai Ni & Yinuo Wang & Kai Yao & Ling Wang & Jiancheng Huang & Yongfang Xiao & Hongyao Chen & Bo Liu & Cliff Y. Yang & Jijun Zhao, 2024. "Cyclical palmitoylation regulates TLR9 signalling and systemic autoimmunity in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Chao Yang & Mahesh Bachu & Yong Du & Caroline Brauner & Ruoxi Yuan & Marie Dominique Ah Kioon & Giancarlo Chesi & Franck J. Barrat & Lionel B. Ivashkiv, 2022. "CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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