Inducible Co-Stimulator Null MRL-Fas lpr Mice

Zeller, Geraldine C.; Hirahashi, Junichi; Schwarting, Andreas; Sharpe, Arlene H.; Kelley, Vicki Rubin

doi:10.1681/asn.2005080802

Cited by 23 publications

(24 citation statements)

References 43 publications

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“…Anti-ICOS mAb co-stimulated peripheral blood lymphocyte cells in the presence of suboptimal concentrations of anti-CD3 mAb signiWcantly enhanced the production of anti-dsDNA antibodies and total IgG in patients with SLE [17,34]. Our study demonstrated that ICOS expression on LN patients was increased as compared with patients without nephritis and normal controls, the results were similar to the study of Zeller et al [20] in mice model. Nevertheless, no correlation was found between ICOS expression and anti-dsDNA antibody.…”

Section: Discussionsupporting

confidence: 90%

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Expression of inducible co-stimulator on peripheral blood T lymphocytes in patients with lupus nephritis

Pan

Chen

et al. 2011

Rheumatol Int

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Systemic lupus erythematosus (SLE) is a complex autoimmune disease and lupus nephritis (LN) represents a major clinical manifestation. Studies have shown that elevated inducible co-stimulator (ICOS) in SLE. The purpose of the study was to investigate the expression of ICOS on T cells in patients with LN. Flow cytometry (FCM) was used to analyze the expression of ICOS on peripheral blood T lymphocytes in LN patients, SLE patients without nephritis, and healthy controls. The expression of ICOS on CD4 + CD45RO + and CD8 + CD4RO + T cells was significantly increased in SLE patients when compared with healthy controls (P < 0.001). In addition, ICOS expression in patients with nephritis was higher than those without nephritis (P < 0.01). Taken together, our results suggest that ICOS co-stimulatory pathway is important in the pathogenesis of LN; blockade of the pathway might represent a novel therapeutic strategy for the treatment of LN.

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Section: Discussionsupporting

confidence: 90%

“…In SLE patients, ICOS expression on CD4 + and CD8 + T cell was higher than normal controls [17,18]. In MRL-Faslpr mice model, ICOS expression in kidneys of mice with nephritis was higher than that without nephritis [20]. However, there are few studies focusing on the role of ICOS in patients with LN.…”

Section: Introductionmentioning

confidence: 99%

Expression of inducible co-stimulator on peripheral blood T lymphocytes in patients with lupus nephritis

Pan

Chen

et al. 2011

Rheumatol Int

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“…Moreover, autoantibody production and tissue inflammation do not seem to be correlated in lupus nephritis. In mice, ICOS-deficient MRL/lpr mice showed significant decrease of each isotype of autoantibody as compared with wild-type mice, but severe renal pathology including glomerulonephritis and interstitial inflammation was comparable(46). There is also evidence that tubulointerstitial inflammation aside from glomerulonephritis is an important prognostic factor for renal outcome(47).…”

Section: Discussionmentioning

confidence: 99%

IL-2 Protects Lupus-Prone Mice from Multiple End-Organ Damage by Limiting CD4−CD8− IL-17–Producing T Cells

Mizui

Koga

Lieberman

et al. 2014

The Journal of Immunology

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Interleukin-2 (IL-2), a cytokine with pleiotropic effects, is critical for immune cell activation and peripheral tolerance. Although the therapeutic potential of IL-2 has been previously suggested in autoimmune diseases, the mechanisms whereby IL-2 mitigates autoimmunity and prevents organ damage remains unclear. Using an inducible recombinant adeno-associated virus (rAAV) vector we investigated the effect of low systemic levels of IL-2 in lupus-prone MRL/Faslpr/lpr (MRL/lpr) mice. Treatment of mice after the onset of disease with IL-2-rAAV resulted in reduced mononuclear cell infiltration and pathology of various tissues including skin, lungs and kidneys. In parallel, we noted a significant decrease of IL-17-producing CD3+CD4−CD8− double-negative T cells and an increase in CD4+CD25+Foxp3+ immunoregulatory T cells (Treg) in the periphery. We also show that IL-2 can drive DN T cell death through an indirect mechanism. Notably, targeted delivery of IL-2 to CD122+ cytotoxic lymphocytes effectively reduced the number of DN T cells and lymphadenopathy whereas selective expansion of Treg by IL-2 had no effect on DN T cells. Collectively, our data suggest that administration of IL-2 to lupus-prone mice protects against end-organ damage and suppresses inflammation by dually limiting IL-17-producing DN T cells and expanding Treg.

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“…Aberrant expression and/or function of T FH -related molecules are associated with lupus-like disease in mice [54, 70]. Similarly, in lupus patients, numbers of molecules involved in T FH generation and/or regulation have been described to be dysregulated.…”

Section: Molecules And/or Cytokines Involved In Tfh Generation/regmentioning

confidence: 99%

Follicular Helper T Cells in Systemic Lupus Erythematosus: Why Should They Be Considered as Interesting Therapeutic Targets?

Sawaf

Dumortier

Monneaux

2016

Journal of Immunology Research

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B cell hyperactivity leading to the production of autoantibodies, some of which having a deleterious effect. Reducing autoantibody production thus represents a way of controlling lupus pathogenesis, and a better understanding of the molecular and cellular factors involved in the differentiation of B cells into plasma cells could allow identifying new therapeutic targets. Follicular helper T cells (TFH) represent a distinct subset of CD4+ T cells specialized in providing help to B cells. They are required for the formation of germinal centers and the generation of long-lived serological memory and, as such, are suspected to play a central role in SLE. Recent advances in the field of TFH biology have allowed the identification of important molecular factors involved in TFH differentiation, regulation, and function. Interestingly, some of these TFH-related molecules have been described to be dysregulated in lupus patients. In the present review, we give an overview of the aberrant expression and/or function of such key players in lupus, and we highlight their potential as therapeutic targets.

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Inducible Co-Stimulator Null MRL-Fas lpr Mice

Cited by 23 publications

References 43 publications

Expression of inducible co-stimulator on peripheral blood T lymphocytes in patients with lupus nephritis

Expression of inducible co-stimulator on peripheral blood T lymphocytes in patients with lupus nephritis

IL-2 Protects Lupus-Prone Mice from Multiple End-Organ Damage by Limiting CD4−CD8− IL-17–Producing T Cells

Follicular Helper T Cells in Systemic Lupus Erythematosus: Why Should They Be Considered as Interesting Therapeutic Targets?

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