{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T04:23:32Z","timestamp":1728447812895},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Naturally occurring CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> regulatory T (Treg) cells are central to the maintenance of peripheral tolerance. Impaired activity and\/or a lower frequency of these cells lead to systemic lupus erythematosus (SLE). Manipulating the number or activity of Treg cells is to be a promising strategy in treating it and other autoimmune diseases. We have examined the effects of Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, on SLE-like symptoms in MRL\/<jats:italic>lpr<\/jats:italic> autoimmune mice and BDF1 hybrid mice. Whether the beneficial effect of Y27 involves modulation of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> Treg cells has also been investigated.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Female MRL\/<jats:italic>lpr<\/jats:italic> mice that spontaneously develop lupus were treated orally by gavage with Y27 for 10 weeks, starting at 10 weeks of age. BDF1 mice developed a chronic graft-versus-host disease (GVHD) by two weekly intravenous injections of parental female DBA\/2 splenic lymphocytes, characterized by immunocomplex-mediated glomerulonephritis resembling SLE. Y27 was administered to chronic GVHD mice for 12 weeks. Nephritic symptoms were monitored and the percentage of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> Treg peripheral blood leukocyte was detected with mouse regulatory T cell staining kit by flowcytometry. Purified CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> Tregs were assessed for immune suppressive activity using the mixed lymphocyte reaction.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>The life-span of MRL\/lpr mice treated with Y27 for 10 weeks was significantly prolonged, proteinuria and renal lesion severity were ameliorated, and blood urea nitrogen, triglyceride and serum anti-double-stranded DNA antibodies were decreased. Similar results were found in chronic GVHD mice. Administration of Y27 had little impact on percentage of the peripheral blood lymphocyte CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> Treg cells in both groups of mice. In contrast, the suppressive capacity of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> Treg cells in splenocytes was markedly augmented in Y27-treated mice <jats:italic>ex vivo<\/jats:italic>.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Experimental evidence of the protect effects of Y27 against autoimmune nephritis has been shown. The mechanism may involve enhancement of the suppressive capacity of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> Treg cells.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar4078","type":"journal-article","created":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T15:14:28Z","timestamp":1351782868000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, prevents the development of murine systemic lupus erythematosus-like diseases in MRL\/lpr autoimmune mice and BDF1 hybrid mice"],"prefix":"10.1186","volume":"14","author":[{"given":"Zhi-Yong","family":"Xiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao-Hui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Ping","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Xia","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Xiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ri-Fang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu-Hong","family":"Yun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,11,1]]},"reference":[{"key":"3829_CR1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0165-2478(98)00113-8","volume":"67","author":"R Nezlin","year":"1999","unstructured":"Nezlin R, Dayan M, Zinger H, Mozes E: DNA levels in immune complexes circulating in mice with induced systemic lupus erythematosus. 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