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Title: | Endogenous Tim-1 promotes severe systemic autoimmunity and renal disease MRL-Faslpr mice. | Authors: | Nozaki Y.;Richard Kitching A.;Akiba H.;Yagita H.;Kinoshita K.;Funauchi M.;Matsumura I. | Institution: | (Nozaki, Kinoshita, Funauchi, Matsumura) Department of Hematology and Rheumatology, Kinki University School of Medicine, Osaka, Japan (Richard Kitching) Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, VIC, Australia (Richard Kitching) Departments of Nephrology and Pediatric Nephrology, Monash Medical Centre, Clayton, VIC, Australia (Akiba, Yagita) Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan | Issue Date: | 2-Jun-2014 | Copyright year: | 2014 | Publisher: | American Physiological Society (E-mail: subscrip@the-aps.org) | Place of publication: | United States | Publication information: | American Journal of Physiology - Renal Physiology. 306 (10) (pp F1210-F1221), 2014. Date of Publication: 2014. | Journal: | American Journal of Physiology - Renal Physiology | 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-Faslpr mice. MRL-Faslpr 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. © 2014 the American Physiological Society. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1152/ajprenal.00570.2013 | Link to associated publication: | Click here for full text options | PubMed URL: | 24623145 [http://www.ncbi.nlm.nih.gov/pubmed/?term=24623145] | ISSN: | 0363-6127 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/41997 | Type: | Article | Subjects: | priority journal protein expression proteinuria regulatory T lymphocyte skin defect spleen survival Th1 cell Th17 cell urinary excretion CCL1 chemokine/ec [Endogenous Compound] CD19 antigen/ec [Endogenous Compound] CD4 antigen/ec [Endogenous Compound] CD5 antigen/ec [Endogenous Compound] complement component C3/ec [Endogenous Compound] CXCL1 chemokine/ec [Endogenous Compound] CXCL2 chemokine/ec [Endogenous Compound] CXCL9 chemokine/ec [Endogenous Compound] DNA antibody gamma interferon inducible protein 10/ec [Endogenous Compound] immunoglobulin/ec [Endogenous Compound] intercellular adhesion molecule 1/ec [Endogenous Compound] interleukin 10/ec [Endogenous Compound] interleukin 12p40/ec [Endogenous Compound] interleukin 17/ec [Endogenous Compound] interleukin 1beta/ec [Endogenous Compound] interleukin 2 receptor alpha/ec [Endogenous Compound] *kidney injury molecule 1/ec [Endogenous Compound] macrophage inflammatory protein 3alpha/ec [Endogenous Compound] messenger RNA/ec [Endogenous Compound] *monoclonal antibody/dt [Drug Therapy] *monoclonal antibody/ip [Intraperitoneal Drug Administration] retinoid related orphan receptor gamma/ec [Endogenous Compound] transcription factor GATA 3/ec [Endogenous Compound] tumor necrosis factor/ec [Endogenous Compound] unclassified drug *rmt 1 10/dt [Drug Therapy] *rmt 1 10/ip [Intraperitoneal Drug Administration] transcription factor FOXP3/ec [Endogenous Compound] animal experiment animal tissue antibody blood level article B lymphocyte cell proliferation controlled study cytokine production female fluorescence activated cell sorting kidney *kidney disease kidney function leukocyte *lupus erythematosus nephritis/dt [Drug Therapy] lupus erythematosus nephritis/dt [Drug Therapy] lymphadenopathy mouse nonhuman kidney *kidney disease kidney function leukocyte *lupus erythematosus nephritis / *drug therapy lupus erythematosus nephritis / drug therapy lymphadenopathy mouse nonhuman priority journal protein expression proteinuria regulatory T lymphocyte skin defect spleen controlled study Th1 cell Th17 cell urinary excretion cell proliferation B lymphocyte article antibody blood level animal tissue animal experiment survival cytokine production female fluorescence activated cell sorting |
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