title: Endogenous Tim-1 promotes severe systemic autoimmunity and renal disease MRL-Fas(lpr) mice.
abstract: The T-cell immunoglobulin mucin 1, also known as kidney injury molecule-1, modulates CD4+ T-cell responses and is also expressed by damaged proximal tubules within the kidney. Both Th subset imbalance (Th1/Th2/Th17) and regulatory T-cell and B-cell alterations contribute to the pathogenesis of autoimmune disease. This study investigated the effects of an inhibitory anti-T-cell immunoglobulin mucin 1 antibody (RMT1-10) in lupus-prone MRL-Fas(lpr) mice. MRL-Fas(lpr) mice were treated with RMT1-10 or a control antibody intraperitoneally twice weekly from 3 mo of age for 16 wk. RMT1-10 treatment significantly improved survival, limited the development of lymphadenopathy and skin lesions, preserved renal function and decreased proteinuria, reduced serum anti-DNA antibody levels, and attenuated renal leukocyte accumulation. Th1 and Th17 cellular responses systemically and intrarenally were reduced, but regulatory T and B cells were increased. RMT1-10 treatment also reduced glomerular immunoglobulin and C3 deposition and suppressed cellular proliferation and apoptosis. Urinary excretion and renal expression of kidney injury molecule-1 was reduced, reflecting diminished interstitial injury. As RMT1-10 attenuated established lupus nephritis, manipulating immune system T-cell immunoglobulin mucin 1 may represent a therapeutic strategy in autoimmune diseases affecting the kidney.
authors.affiliation: Department of Hematology and Rheumatology, Kinki University School of Medicine, Osaka, Japan; yuji0516@med.kindai.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nozaki
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Victoria, Australia; Departments of Nephrology and Pediatric Nephrology, Monash Medical Centre, Clayton, Victoria, Australia; and.
authors.forename: A Richard
authors.initials: AR
authors.lastname: Kitching
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Department of Hematology and Rheumatology, Kinki University School of Medicine, Osaka, Japan;
authors.forename: Koji
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: Department of Hematology and Rheumatology, Kinki University School of Medicine, Osaka, Japan;
authors.forename: Masanori
authors.initials: M
authors.lastname: Funauchi
authors.affiliation: Department of Hematology and Rheumatology, Kinki University School of Medicine, Osaka, Japan;
authors.forename: Itaru
authors.initials: I
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000503:physiopathology*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000453:epidemiology / Q000503:physiopathology*; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011507:Proteinuria / Q000517:prevention & control; D012720:Severity of Illness Index
chemical_list: D000888:Antibodies, Anti-Idiotypic; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D008565:Membrane Proteins
keywords: Tim-1; chemokine; cytokine; lupus nephritis