[HTML][HTML] CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis

QQ Huang, H Perlman, R Birkett, R Doyle… - Nature …, 2015 - nature.com
QQ Huang, H Perlman, R Birkett, R Doyle, D Fang, GK Haines, W Robinson, S Datta…
Nature communications, 2015nature.com
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 …
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.
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