CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis

Qi-Quan Huang, Harris R Perlman, Robert Birkett, Renee Doyle, Deyu Fang, G. Kenneth Haines, William Robinson, Syamal Kumar Datta, Zan Huang, Quan Zhen Li, Hyewon Phee, Richard M Pope*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Article number7086
JournalNature communications
Volume6
DOIs
StatePublished - May 12 2015

Fingerprint

arthritis
deletion
Dendritic Cells
Arthritis
T-cells
Regulatory T-Lymphocytes
cells
Rheumatoid Arthritis
mice
Joints
T-Lymphocytes
Macrophages
Immune system
Natural Killer Cells
Autoantibodies
Immune System
Homeostasis
Lymph Nodes
Tissue
homeostasis

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Huang, Qi-Quan ; Perlman, Harris R ; Birkett, Robert ; Doyle, Renee ; Fang, Deyu ; Haines, G. Kenneth ; Robinson, William ; Datta, Syamal Kumar ; Huang, Zan ; Li, Quan Zhen ; Phee, Hyewon ; Pope, Richard M. / CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis. In: Nature communications. 2015 ; Vol. 6.
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CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis. / Huang, Qi-Quan; Perlman, Harris R; Birkett, Robert; Doyle, Renee; Fang, Deyu; Haines, G. Kenneth; Robinson, William; Datta, Syamal Kumar; Huang, Zan; Li, Quan Zhen; Phee, Hyewon; Pope, Richard M.

In: Nature communications, Vol. 6, 7086, 12.05.2015.

Research output: Contribution to journalArticle

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