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Open Access Research article

Sialoadhesin deficiency does not influence the severity of lupus nephritis in New Zealand Black x New Zealand White F1 mice

Dana Kidder1, Hannah E Richards1, Paul A Lyons2 and Paul R Crocker1*

Author Affiliations

1 Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom

2 Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge, Hills Road, Cambridge CB2 0XY, United Kingdom

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Arthritis Research & Therapy 2013, 15:R175  doi:10.1186/ar4364

Published: 1 November 2013

Abstract

Introduction

Systemic lupus erythematosus (SLE) is a chronic inflammatory condition with multisystem involvement. One of the key features of the disease is the upregulation of type I interferons, resulting in the so-called “interferon signature”. Recent flow cytometric and transcriptomic studies identified Sialoadhesin (Sn, CD169) as an important interferon-induced blood monocyte biomarker in diseased patients. To investigate a potential causative role of Sn in SLE, we generated NZBWF1 (New Zealand Black x New Zealand White F1) mice lacking Sn and compared onset and progression of disease with NZBWF1 expressing normal levels of Sn.

Methods

Sn expression in renal tissues of pre-diseased and diseased NZBWF1 mice was evaluated by Quantitative real time PCR (QPCR) and immunohistochemistry. Sn−/− NZBWF1 mice were generated by speed congenics. Disease severity of Sn+/+ and Sn−/− NZBWF1 mice was assessed by serum immunoassays, flow cytometry, light microscopy and immunohistochemistry.

Results

Renal tissues from proteinuric NZBWF1 mice exhibited a significant upregulation of Sn mRNA and protein expression following disease onset. Further immunohistochemical analysis showed that Sn+ macrophages assumed a distinct periglomerular distribution and, unlike CD68+ macrophages, were not present within the glomeruli. Analysis of disease severity in Sn−/− and Sn+/+ NZBWF1 mice revealed no significant differences in the disease progression between the two groups although Sn-deficient mice showed a more rapid onset of proteinuria.

Conclusions

These data confirm a positive correlation of Sn with disease activity. However, Sn deficiency does not have a significant effect on the severity and progression of lupus nephritis in the NZBWF1 mouse model.