{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:34:15Z","timestamp":1792056855169,"version":"4.4.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2003,4,1]],"date-time":"2003-04-01T00:00:00Z","timestamp":1049155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autoimmune disease in MRL-Faslpr mice is characterized by fatal nephritis, systemic pathology, and autoantibodies, mimicking human lupus. We previously reported that 1) intrarenal IL-12 elicits nephritis by fostering the accumulation of intrarenal IFN-\u03b3-secreting T cells, and 2) MRL-Faslpr mice deficient in the IFN-\u03b3 receptor were spared from nephritis. Therefore, we hypothesized that eliminating IL-12 in MRL-Faslpr mice reduces IFN-\u03b3-secreting cells and thereby prevents systemic pathology. For this purpose, we constructed an IL-12p40-deficient MRL-Faslpr(IL-12\u2212\/\u2212) strain. We determined that glomerular and interstitial, but not perivascular, renal pathology were decreased in IL-12\u2212\/\u2212 mice vs the wild-type (WT) strain (5 mo of age). Similarly, systemic pathology (lung, lacrimal and salivary glands, skin, and lymphadenopathy) was diminished. The intrarenal accumulation of T cells (CD4+, CD8+, CD4\u2212CD8\u2212B220+) and macrophages was dramatically reduced in IL-12\u2212\/\u2212 MRL-Faslpr kidneys. We determined that there were fewer IFN-\u03b3 transcripts (&amp;gt;70%) in the IL-12\u2212\/\u2212 protected kidneys compared with the WT kidneys. Similarly, cells propagated from IL-12\u2212\/\u2212 MRL-Faslpr kidneys generated substantially less IFN-\u03b3 when stimulated with IL-12 and IL-18 compared with those from WT kidneys, and we detected fewer CD8 and B220 T cells producing IFN-\u03b3 in these IL-12\u2212\/\u2212 MRL-Faslpr kidneys. Of note, survival was modestly extended in the IL-12\u2212\/\u2212 MRL-Faslpr mice. While lung and lacrimal and salivary gland pathology remained reduced in moribund IL-12\u2212\/\u2212 MRL-Faslpr mice, renal pathology and IFN-\u03b3 expression were equivalent to those in the WT strain. Thus, we suggest that IL-12 is a therapeutic target for multiple tissues in lupus; however blocking IL-12 alone is not sufficient to confer enduring protection from lupus nephritis.<\/jats:p>","DOI":"10.4049\/jimmunol.170.7.3915","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:28:40Z","timestamp":1398022120000},"page":"3915-3925","source":"Crossref","is-referenced-by-count":136,"title":["IL-12 Deficiency in MRL-\n                    <i>Fas<\/i>\n                    <i>lpr<\/i>\n                    Mice Delays Nephritis and Intrarenal IFN-\u03b3 Expression, and Diminishes Systemic Pathology"],"prefix":"10.1093","volume":"170","author":[{"given":"Eriya","family":"Kikawada","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Autoimmune Disease, Renal Division, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M","family":"Lenda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Autoimmune Disease, Renal Division, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki R","family":"Kelley","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Autoimmune Disease, Renal Division, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,4,1]]},"reference":[{"key":"2026020210072235600_R1","first-page":"179","volume-title":"Immunol. 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Immunol.","year":"1989"},{"key":"2026020210072235600_R12","first-page":"4135","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210072235600_R13","first-page":"547","volume-title":"Science","year":"1993"},{"key":"2026020210072235600_R14","first-page":"1387","volume-title":"J. Exp. Med.","year":"1992"},{"key":"2026020210072235600_R15","first-page":"335","volume-title":"Immunol. Today","year":"1993"},{"key":"2026020210072235600_R16","first-page":"874","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020210072235600_R17","first-page":"3495","volume-title":"J. Immunol.","year":"1992"},{"key":"2026020210072235600_R18","first-page":"869","volume-title":"J. Exp. Med.","year":"1991"},{"key":"2026020210072235600_R19","first-page":"1597","volume-title":"J. Clin. Invest.","year":"1996"},{"key":"2026020210072235600_R20","first-page":"389","volume-title":"Clin. Exp. Immunol.","year":"1998"},{"key":"2026020210072235600_R21","first-page":"10188","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1993"},{"key":"2026020210072235600_R22","first-page":"1447","volume-title":"J. Exp. Med.","year":"1996"},{"key":"2026020210072235600_R23","first-page":"827","volume-title":"J. Exp. Med.","year":"1989"},{"key":"2026020210072235600_R24","first-page":"6808","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1990"},{"key":"2026020210072235600_R25","first-page":"3433","volume-title":"J. Immunol.","year":"1992"},{"key":"2026020210072235600_R26","first-page":"3074","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020210072235600_R27","first-page":"4143","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1991"},{"key":"2026020210072235600_R28","first-page":"471","volume-title":"Immunity","year":"1996"},{"key":"2026020210072235600_R29","first-page":"429","volume-title":"Immunity","year":"2002"},{"key":"2026020210072235600_R30","first-page":"433","volume-title":"J. Immunol.","year":"1996"},{"key":"2026020210072235600_R31","first-page":"4074","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020210072235600_R32","first-page":"18","volume-title":"J. Mol. Recognit.","year":"2001"},{"key":"2026020210072235600_R33","first-page":"1713","volume-title":"J. Exp. Med.","year":"1988"},{"key":"2026020210072235600_R34","first-page":"1441","volume-title":"J. Exp. Med.","year":"1991"},{"key":"2026020210072235600_R35","first-page":"6509","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020210072235600_R36","first-page":"1198","volume-title":"J. Exp. Med.","year":"1978"},{"key":"2026020210072235600_R37","first-page":"157","volume-title":"Arthritis Rheum.","year":"1984"},{"key":"2026020210072235600_R38","first-page":"207","volume-title":"J. Clin. Invest.","year":"2000"},{"key":"2026020210072235600_R39","first-page":"3400","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020210072235600_R40","first-page":"297","volume-title":"Mol. Med.","year":"1996"},{"key":"2026020210072235600_R41","first-page":"1936","volume-title":"J. Clin. Invest.","year":"1997"},{"key":"2026020210072235600_R42","first-page":"427","volume-title":"J. Immunol.","year":"1996"},{"key":"2026020210072235600_R43","first-page":"2985","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210072235600_R44","first-page":"3","volume-title":"Clin. Exp. Immunol.","year":"1997"},{"key":"2026020210072235600_R45","first-page":"298","volume-title":"Dig. Dis.","year":"1993"},{"key":"2026020210072235600_R46","first-page":"423","volume-title":"Crit. Rev. Clin. Lab. Sci.","year":"1996"},{"key":"2026020210072235600_R47","first-page":"2653","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210072235600_R48","first-page":"339","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026020210072235600_R49","first-page":"5366","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020210072235600_R50","first-page":"493","volume-title":"J. Cell Physiol.","year":"1998"},{"key":"2026020210072235600_R51","first-page":"7","volume-title":"J. Infect. 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