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 and Richard M. Pope ()
Additional contact information
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

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms8086 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8086

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8086

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().