| First Author | Huang QQ | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7086 | PubMed ID | 25963626 |
| Mgi Jnum | J:224881 | Mgi Id | MGI:5689236 |
| Doi | 10.1038/ncomms8086 | Citation | Huang QQ, et al. (2015) CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis. Nat Commun 6:7086 |
| abstractText | 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 CD8alpha(+) 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 CD8alpha(+) DCs and other cells of the immune system. |
