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CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis NATURE COMMUNICATIONS Huang, Q., Perlman, H., Birkett, R., Doyle, R., Fang, D., Haines, G. K., Robinson, W., Datta, S., Huang, Z., Li, Q., Phee, H., Pope, R. M. 2015; 6

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 CD8a(+) 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 CD8a(+) DCs and other cells of the immune system.

View details for DOI 10.1038/ncomms8086

View details for PubMedID 25963626