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CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis

Author

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  • Qi-Quan Huang

    (Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA)

  • Harris Perlman

    (Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA)

  • Robert Birkett

    (Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA)

  • Renee Doyle

    (Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA)

  • Deyu Fang

    (Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA)

  • G. Kenneth Haines

    (Mount Sinai Hospital School of Medicine)

  • William Robinson

    (Stanford University School of Medicine, VA Health Care System, Palo Alto, California 94304, USA)

  • Syamal Datta

    (Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA)

  • Zan Huang

    (College of Life Sciences, Wuhan University)

  • Quan-Zhen Li

    (University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA)

  • Hyewon Phee

    (Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA)

  • Richard M. Pope

    (Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA)

Abstract

Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive, inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically reduced when these mice are crossed with Rag−/− mice. The CD8α+ DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4+ T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4+ T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory cells (Tregs) inversely correlate with arthritis severity, and the transfer of Tregs ameliorates arthritis. This KO line identifies a model that will permit in depth interrogation of the pathogenesis of rheumatoid arthritis, including the role of CD8α+ DCs and other cells of the immune system.

Suggested Citation

  • Qi-Quan Huang & Harris Perlman & Robert Birkett & Renee Doyle & Deyu Fang & G. Kenneth Haines & William Robinson & Syamal Datta & Zan Huang & Quan-Zhen Li & Hyewon Phee & Richard M. Pope, 2015. "CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8086
    DOI: 10.1038/ncomms8086
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