In:
American Journal of Nephrology, S. Karger AG, Vol. 46, No. 5 ( 2017), p. 371-379
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Systemic lupus erythematosus (SLE) is characterized by abnormal activated T cells, autoreactive B cells, and massive cytokines. The CD4+ T cells determined B-cells differentiation and cytokines production. The programmed death 1 (PD-1) is the checkpoint immunoinhibitory receptor of activated T cells, and its engagement could exhaust T cells. In this study, we investigated the role of PD-1 systemic engagement with PD-L1-Ig in lupus-like nephritis in SLE mice. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The murine PD-L1-Ig was injected into SLE-prone mice. The proteinuria and survival ratio were monitored. The production of anti-dsDNA autoantibodies and cytokines in serum were measured by enzyme-linked immunosorbent assay. The cytokine-producing T cells (interferon- & #x03B3;, IFN- & #x03B3; and IL-17α) in kidney and spleen were detected with flowcytometry. The pathological evaluation of the Ig deposition in the glomeruliand was determined with immunofluorescence. Lymphocytes in 24-h urine were detected with flowcytometry. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The systemic administration of PD-L1-Ig activated PD-1-PD-L1 axis of CD4+ T lymphocytes, suppressed Th17 formation in many organs, including the spleen and the kidney, demolished abnormal production of cytokines (IFN- & #x03B3;, IL-17, and IL-10) and anti-dsDNA autoantibodies in serum, inhibited immunoglobulin G deposition in the glomeruli with the decrease of proteinuria, and activated T cells in urine. Accordingly, the systemic conjugation of PD-L1-PD-1 impaired renal autoimmune injure and prolonged survival time. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our research demonstrated that the protective function of systemic activation of PD-1-PD-L1 axis with PD-L1-Ig attenuates the nephritis in SLE-prone mice, which facilitates us to understand the suppressive function of PD-1-PD-L1 axis in the pathogenesis and progress of the lupus nephritis, and to explore a possible effective therapeutic strategy to SLE.
Type of Medium:
Online Resource
ISSN:
0250-8095
,
1421-9670
Language:
English
Publisher:
S. Karger AG
Publication Date:
2017
detail.hit.zdb_id:
1468523-1
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