Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms8086
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Funding
- NIH [AR048269, AR065076, AR064464, HL108795, AR050250, AR054796, AR055503, AI067590, AI041985, AI079056, AI108634, AR006634, AR059754]
- Solovy Arthritis Research Society
- ACR RRF
- Israel Binational Foundation
- Northwestern University Mouse Histology and Phenotyping Laboratory
- Cancer Center Support Grant (NCI) [CA060553]
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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 CD8 alpha(+) 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 CD8 alpha(+) DCs and other cells of the immune system.
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