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

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Arthritis Research and Therapy

, 15:R175

First Online: 01 November 2013Received: 20 July 2013Accepted: 11 October 2013


IntroductionSystemic 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.

MethodsSn 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.

ResultsRenal 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.

ConclusionsThese 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.

AbbreviationsBSABovine serum albumin

EAEExperimental autoimmune encephalomyelitis

EDTAEthylenediaminetetraacetic acid

ELISAEnzyme-linked immunosorbent assay

FACSFluorescence-activated cell sorting

gcsGlomerular cross-section

HandEHaematoxylin and eosin

HRPHorse radish peroxidase



NZBNew Zealand black

NZBWF1New Zealand black x New Zealand white F1

NZWNew Zealand white

PBSPhosphate-buffered saline

PBSTPhosphate-buffered saline plus 0.05% Tween

qRT-PCRQuantitative reverse transcriptase-polymerase chain reaction

SLESystemic lupus erythematosus


SnLSn ligands

TeffsCD4 + Foxp3-effector T cells

TNFTumour necrosis factor

TregsCD4 + Foxp3+ regulatory T cells


Electronic supplementary materialThe online version of this article doi:10.1186-ar4364 contains supplementary material, which is available to authorized users.

Dana Kidder, Hannah E Richards contributed equally to this work.

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Autor: Dana Kidder - Hannah E Richards - Paul A Lyons - Paul R Crocker


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