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TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus

Author

Listed:
  • Cristiana Guiducci

    (Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, California 94710, USA)

  • Mei Gong

    (Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, California 94710, USA)

  • Zhaohui Xu

    (Baylor Institute for Immunology Research, Dallas, Texas 75204, USA)

  • Michelle Gill

    (Baylor Institute for Immunology Research, Dallas, Texas 75204, USA
    †Present address: University of Texas, Southwestern Medical Center, Dallas, Texas 75235, USA.)

  • Damien Chaussabel

    (Baylor Institute for Immunology Research, Dallas, Texas 75204, USA)

  • Thea Meeker

    (Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, California 94710, USA)

  • Jean H. Chan

    (Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, California 94710, USA)

  • Tracey Wright

    (Texas Scottish Rite Hospital, Dallas, Texas 75219, USA
    University of Texas, Southwestern Medical Center and Children’s Medical Center, Dallas, Texas 75235, USA)

  • Marilynn Punaro

    (Texas Scottish Rite Hospital, Dallas, Texas 75219, USA
    University of Texas, Southwestern Medical Center and Children’s Medical Center, Dallas, Texas 75235, USA)

  • Silvia Bolland

    (Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA)

  • Vassili Soumelis

    (Institut Curie, 26 rue d’Ulm, 75005 Paris, France)

  • Jacques Banchereau

    (Baylor Institute for Immunology Research, Dallas, Texas 75204, USA)

  • Robert L. Coffman

    (Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, California 94710, USA)

  • Virginia Pascual

    (Baylor Institute for Immunology Research, Dallas, Texas 75204, USA
    Texas Scottish Rite Hospital, Dallas, Texas 75219, USA)

  • Franck J. Barrat

    (Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, California 94710, USA)

Abstract

Corticosteroid boost in lupus Systemic lupus erythematosus (SLE) is an autoimmune disease in which innate tolerance to self nucleic acids is broken with devastating consequences. There have been few advances in therapy in recent years, and patients are still treated mostly with strong immunosuppressives such as high-dose glucocorticoids, often causing severe side effects. In fact lupus patients require much higher glucocorticoid doses than needed in other autoimmune diseases such as rheumatoid arthritis. A possible explanation for this low sensitivity to glucocorticoids has now been identified. In SLE patients the Toll-like receptors TLR7 and TLR9, key players in innate immunity, recognize self nucleic acids on B cells and plasmacytoid dendritic cells (PDC). Now it is shown that, in SLE patients and in lupus-prone mouse strains, stimulation of PDCs by TLR7/9 reduces the immuosuppressive potency of glucocorticoids. This suggests that inhibitors of TLR7/9 signalling, such as the novel class of oligonucleotides known as immunoregulatory sequences (IRSs), could prove to be effective corticosteroid-sparing drugs.

Suggested Citation

  • Cristiana Guiducci & Mei Gong & Zhaohui Xu & Michelle Gill & Damien Chaussabel & Thea Meeker & Jean H. Chan & Tracey Wright & Marilynn Punaro & Silvia Bolland & Vassili Soumelis & Jacques Banchereau &, 2010. "TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus," Nature, Nature, vol. 465(7300), pages 937-941, June.
    • Handle: RePEc:nat:nature:v:465:y:2010:i:7300:d:10.1038_nature09102
    DOI: 10.1038/nature09102
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