{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:52:23Z","timestamp":1790218343493,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,9,24]],"date-time":"2013-09-24T00:00:00Z","timestamp":1379980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that is characterized by the production of antinuclear antibodies (ANAs) and leads to immune complex deposition in the kidneys and nephritis. Lyn tyrosine kinase is a regulator of antibody\u2010mediated autoimmune disease, as evidenced by studies in gene\u2010targeted mice and as suggested in genome\u2010wide association studies in SLE. Like SLE patients, Lyn\u2010deficient mice have increased levels of interleukin\u20106 (IL\u20106). Deletion of IL\u20106 from Lyn\u2010deficient mice abrogates levels of inflammation, pathogenic autoantibodies, and nephritis. The purpose of this study was to assess the role of IL\u20106 <jats:italic>trans<\/jats:italic>\u2010signaling in autoimmune disease by overexpressing soluble gp130Fc (sgp130Fc) in a mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effect of overexpression of sgp130Fc on immune cell phenotypes was determined by flow cytometry in young and aged mice with lupus, and ANAs were measured by enzyme\u2010linked immunosorbent assay. Glomerulonephritis was assessed by histopathologic analysis, by measuring the glomerular area and the blood urea nitrogen concentration, and by immunohistochemistry. Immunofluorescence defined renal immune complex and complement deposition. The acute\u2010phase response was determined by quantitative real\u2010time polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In contrast to removing IL\u20106, impaired IL\u20106 <jats:italic>trans<\/jats:italic>\u2010signaling had little effect on many immune cell abnormalities in Lyn<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Pathogenic ANAs and kidney deposition of immune complexes were also unaltered by sgp130Fc. However, sgp130Fc overexpression led to diminished macrophage expansion, reduced glomerular leukocyte infiltration, reduced complement fixation, significantly attenuated glomerulonephritis, and improved renal function in Lyn\u2010deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results reveal key roles of leukocytes, complement, and the innate immune system in mediating glomerulonephritis, and they implicate IL\u20106 <jats:italic>trans<\/jats:italic>\u2010signaling in this process. We suggest that targeting this pathway may be an effective adjunct to B cell depletion in SLE treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38061","type":"journal-article","created":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T20:57:45Z","timestamp":1372712265000},"page":"2691-2702","source":"Crossref","is-referenced-by-count":52,"title":["Interleukin\u20106 <i>Trans<\/i>\u2010Signaling Exacerbates Inflammation and Renal Pathology in Lupus\u2010Prone Mice"],"prefix":"10.1002","volume":"65","author":[{"given":"Evelyn","family":"Tsantikos","sequence":"first","affiliation":[{"name":"Monash University, Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mhairi J.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Monash University, Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Putoczki","sequence":"additional","affiliation":[{"name":"Ludwig Institute for 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