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: Yuji Nozaki, A Richard Kitching, Hisaya Akiba, Hideo Yagita, Koji Kinoshita, Masanori Funauchi, Itaru Matsumura
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 306 Issue 10 Pg. F1210-21 (May 15 2014) ISSN: 1522-1466 [Electronic] United States
• PMID: 24623145 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• Antibodies, Anti-Idiotypic
• Havcr1 protein, mouse
• Hepatitis A Virus Cellular Receptor 1
• Membrane Proteins

Topics

• Animals
• Antibodies, Anti-Idiotypic (immunology, pharmacology)
• Apoptosis (drug effects)
• Autoimmune Diseases (epidemiology, physiopathology)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Female
• Hepatitis A Virus Cellular Receptor 1
• Kidney (pathology)
• Kidney Diseases (epidemiology, physiopathology)
• Lupus Erythematosus, Systemic (physiopathology)
• Membrane Proteins (antagonists & inhibitors, immunology, physiology)
• Mice
• Mice, Inbred MRL lpr
• Proteinuria (prevention & control)
• Severity of Illness Index