{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:44:50Z","timestamp":1790783090067,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"45","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,11,9]]},"abstract":"<jats:p>\n                    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\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    macrophages were responsible for triggering arthritis, and their lymphocytes worked protectively. A high level of TNF\u03b1, IL-1\u03b2, 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 TNF\u03b1, IL-1\u03b2, or IL-6 gene blocked the expression of the other cytokine genes as well and inhibited the development of arthritis. Neutralization of TNF\u03b1, IL-1\u03b2, 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1010603107","type":"journal-article","created":{"date-parts":[[2010,10,26]],"date-time":"2010-10-26T00:46:40Z","timestamp":1288054000000},"page":"19432-19437","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":105,"title":["Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation"],"prefix":"10.1073","volume":"107","author":[{"given":"Kohki","family":"Kawane","sequence":"first","affiliation":[{"name":"Department of Medical Chemistry, Kyoto University Graduate School of Medicine, Kyoto 606-8501, 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