Multitarget Therapy of Lupus Nephritis

Glassock, Richard J.

doi:10.1681/asn.2008070779

Cited by 6 publications

(2 citation statements)

References 14 publications

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“…Sle1.lpr and B6. Sle2c1.lpr strains, represent valuable systems in which to examine the varied mechanisms of tissue injury, genetics, and more specific therapeutic modalities (35).…”

Section: Discussionmentioning

confidence: 99%

The NZM2410-derived lupus susceptibility locus Sle2c1 increases Th17 polarization and induces nephritis in fas-deficient mice

Xu¹,

Cuda²,

Croker³

et al. 2011

Arthritis & Rheumatism

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Objective. Sle2 is a lupus susceptibility locus that has been linked to glomerulonephritis in the NZM2410 mouse. By itself, Sle2 does not induce any autoimmune pathology but results in the accumulation of B-1a cells. This study was designed to assess the contribution of Sle2 to the pathogenesis of autoimmunity.Methods. Sle2 or its subcongenic intervals (Sle2a, Sle2b, and Sle2c1) were bred to Fas-deficient B6.lpr mice. Lymphoid phenotypes, which were focused on T cells, were assessed by flow cytometry, and histopathologic changes were compared between cohorts of B6.Sle2.lpr congenic mice and B6.lpr mice of ages up to 6 months.Results. Sle2 synergized with lpr, resulting in a greatly accelerated lymphadenopathy that largely targeted T cells and mapped to the Sle2c1 locus. This locus has been identified as the main contributor to B-1a cell expansion. Further analyses showed that Sle2c1 expression skewed the differentiation and polarization of Fasdeficient T cells, with a reduction of the CD4؉CD25؉ FoxP3؉ regulatory T cell subset and an expansion of the Th17 cells. This was associated with a high number of T cell infiltrates that promoted severe nephritis and dermatitis in the B6.Sle2c1.lpr mice.Conclusion. These results show that Sle2c1 contributes to lupus pathogenesis by affecting T cell differentiation in combination with other susceptibility loci, such as lpr. The significance of the cosegregation of this phenotype and B-1a cell expansion in Sle2c1-expressing mice in relation to the pathogenesis of lupus is discussed.

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“…Sle1.lpr and B6. Sle2c1.lpr strains, represent valuable systems in which to examine the varied mechanisms of tissue injury, genetics, and more specific therapeutic modalities (35).…”

Section: Discussionmentioning

confidence: 99%

The NZM2410-derived lupus susceptibility locus Sle2c1 increases Th17 polarization and induces nephritis in fas-deficient mice

Xu¹,

Cuda²,

Croker³

et al. 2011

Arthritis & Rheumatism

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“…The effect of tacrolimus on T cells may be a critical component of the observed benefits in the study by Bao et al [20] as the severe focal and segmental forms of lupus nephritis have a dominant T cell-dependent pathogenesis [36]. MMF, besides suppressing lymphocyte proliferation and decreasing antibodies formation, can suppress IL-2 production additionally when given with tacrolimus [37].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Cytokine Modulating Effects of Tacrolimus in Systemic Lupus Erythematosus: A Review

Yoon¹

2010

Journal of Biomedicine and Biotechnology

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Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease with involvement of both B cells and cytotoxic T lymphocytes and several cytokines aberrations. Standard therapy for SLE has its limitations. Tacrolimus, a novel calcineurin inhibitor with potent immunosuppressive effects, has been shown in the recent years to be effective in SLE therapy. This paper serves to collate the experimental and clinical data on the efficacy of tacrolimus in the treatment of SLE and lupus nephritis. Tacrolimus as a key component of multitarget therapy in SLE is also discussed. The immunocytokine modulatory effects of tacrolimus are also reviewed with reference to SLE. It can be concluded that tacrolimus has an established role in the management of SLE.

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Lupus Nephritis Clinical Trials: A Critical Appraisal

Glassock

2015

Informing Clinical Practice in Nephrology

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Multitarget Therapy of Lupus Nephritis

Cited by 6 publications

References 14 publications

The NZM2410-derived lupus susceptibility locus Sle2c1 increases Th17 polarization and induces nephritis in fas-deficient mice

The NZM2410-derived lupus susceptibility locus Sle2c1 increases Th17 polarization and induces nephritis in fas-deficient mice

Efficacy and Cytokine Modulating Effects of Tacrolimus in Systemic Lupus Erythematosus: A Review

Lupus Nephritis Clinical Trials: A Critical Appraisal

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