CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis

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

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<sup>-/-</sup> mice. The CD8α<sup>+</sup> DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4<sup>+</sup> T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4<sup>+</sup> 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<sup>+</sup> 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

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

Cite this

Huang, Q. Q., Perlman, H., Birkett, R., Doyle, R., Fang, D., Haines, G. K., ... Pope, R. M. (2015). CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis. Nature Communications, 6, [7086]. https://doi.org/10.1038/ncomms8086

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

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

Research output: Contribution to journalArticle

Huang, QQ, Perlman, H, Birkett, R, Doyle, R, Fang, D, Haines, GK, Robinson, W, Datta, S, Huang, Z, Li, QZ, Phee, H & Pope, RM 2015, 'CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis', Nature Communications, vol. 6, 7086. https://doi.org/10.1038/ncomms8086
Huang, Qi Quan ; Perlman, Harris ; Birkett, Robert ; Doyle, Renee ; Fang, Deyu ; Haines, G. Kenneth ; Robinson, William ; Datta, Syamal ; 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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