| First Author | Kawane K | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 45 | Pages | 19432-7 |
| PubMed ID | 20974942 | Mgi Jnum | J:167378 |
| Mgi Id | MGI:4868148 | Doi | 10.1073/pnas.1010603107 |
| Citation | Kawane K, et al. (2010) Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation. Proc Natl Acad Sci U S A 107(45):19432-7 |
| abstractText | DNase II digests the chromosomal DNA in macrophages after apoptotic cells and nuclei from erythroid precursors are engulfed. The DNase II-null mice develop a polyarthritis that resembles rheumatoid arthritis. Here, we showed that when bone marrow cells from the DNase II-deficient mice were transferred to the wild-type mice, they developed arthritis. A deficiency of Rag2 or a lack of lymphocytes accelerated arthritis of the DNase II-null mice, suggesting that the DNase II(-/-) macrophages were responsible for triggering arthritis, and their lymphocytes worked protectively. A high level of TNFalpha, IL-1beta, and IL-6 was found in the affected joints of the DNase II-null mice, suggesting an inflammatory-skewed cytokine storm was established in the joints. A lack of TNFalpha, IL-1beta, or IL-6 gene blocked the expression of the other cytokine genes as well and inhibited the development of arthritis. Neutralization of TNFalpha, IL-1beta, or IL-6 had a therapeutic effect on the developed arthritis of the DNase II-null mice, indicating that the cytokine storm was essential for the maintenance of arthritis in the DNase II-deficient mice. Methotrexate, an antimetabolite that is often used to treat patients with rheumatoid arthritis, had a therapeutic effect with the DNase II-null mice. These properties of arthritis in the DNase II-null mice were similar to those found in human systemic-onset juvenile idiopathic arthritis or Still's disease, indicating that the DNase II-null mice are a good animal model of this type of arthritis. |
