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

Dana Kidder, Hannah E. Richards, Paul A. Lyons, Paul R. Crocker (Corresponding Author)

Research output: Contribution to journalArticle

4 Citations (Scopus)
4 Downloads (Pure)

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.
Original languageEnglish
Article numberR175
Number of pages9
JournalArthritis Research & Therapy
Volume15
Issue number6
DOIs
Publication statusPublished - 1 Nov 2013

Fingerprint

Sialic Acid Binding Ig-like Lectin 1
Lupus Nephritis
New Zealand
Interferons
Disease Progression
Up-Regulation
Immunohistochemistry
Macrophages
Interferon Type I
Proteinuria
Immunoassay
Real-Time Polymerase Chain Reaction
Monocytes
Microscopy
Flow Cytometry
Biomarkers

Keywords

  • Systemic Lupus Erythematosus
  • Experimental Autoimmune Encephalomyelitis
  • Lupus Nephritis
  • Active Systemic Lupus Erythematosus
  • Histological Severity

Cite this

Sialoadhesin deficiency does not influence the severity of lupus nephritis in New Zealand Black x New Zealand White F1 mice. / Kidder, Dana; Richards, Hannah E.; Lyons, Paul A.; Crocker, Paul R. (Corresponding Author).

In: Arthritis Research & Therapy, Vol. 15, No. 6, R175, 01.11.2013.

Research output: Contribution to journalArticle

@article{9ab69f7a77ab4bb996f64e7b99a92b2c,
title = "Sialoadhesin deficiency does not influence the severity of lupus nephritis in New Zealand Black x New Zealand White F1 mice",
abstract = "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.",
keywords = "Systemic Lupus Erythematosus, Experimental Autoimmune Encephalomyelitis, Lupus Nephritis, Active Systemic Lupus Erythematosus, Histological Severity",
author = "Dana Kidder and Richards, {Hannah E.} and Lyons, {Paul A.} and Crocker, {Paul R.}",
note = "Acknowledgements This work was supported by a Wellcome Trust Clinical Fellowship 087078 (to DK) and Wellcome Trust Senior Fellowship 081882MA (to PRC). PAL was funded by a Wellcome Trust Programme Grant (083650/Z/07/Z). We thank the Renal Unit in Ninewells Hospital, Dundee, Scotland, UK, for their support with the immunohistochemistry analysis.",
year = "2013",
month = "11",
day = "1",
doi = "10.1186/ar4364",
language = "English",
volume = "15",
journal = "Arthritis Research & Therapy",
issn = "1478-6354",
publisher = "BioMed Central",
number = "6",

}

TY - JOUR

T1 - Sialoadhesin deficiency does not influence the severity of lupus nephritis in New Zealand Black x New Zealand White F1 mice

AU - Kidder, Dana

AU - Richards, Hannah E.

AU - Lyons, Paul A.

AU - Crocker, Paul R.

N1 - Acknowledgements This work was supported by a Wellcome Trust Clinical Fellowship 087078 (to DK) and Wellcome Trust Senior Fellowship 081882MA (to PRC). PAL was funded by a Wellcome Trust Programme Grant (083650/Z/07/Z). We thank the Renal Unit in Ninewells Hospital, Dundee, Scotland, UK, for their support with the immunohistochemistry analysis.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - 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.

AB - 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.

KW - Systemic Lupus Erythematosus

KW - Experimental Autoimmune Encephalomyelitis

KW - Lupus Nephritis

KW - Active Systemic Lupus Erythematosus

KW - Histological Severity

U2 - 10.1186/ar4364

DO - 10.1186/ar4364

M3 - Article

VL - 15

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

IS - 6

M1 - R175

ER -