Function of the Th17/interleukin-17A immune response in murine lupus nephritis.
ARTHRITIS & RHEUMATOLOGY(2015)
Abstract
Objective. The CD4+ T cell immune response plays a pivotal role in the immunopathogenesis of human and experimental lupus nephritis, but the contribution of the Th17/interleukin-17 (IL-17) immune pathway to renal tissue injury in systemic lupus erythematosus (SLE) remains to be elucidated. The aim of this study was to characterize the function of the Th17/IL-17A immune response in 2 murine models of lupus nephritis. Methods. IL-17A-deficient MRL/MPJ-Fas(lpr)/2J (MRL/lpr) mice were generated, and the clinical course of nephritis was monitored by assessing the levels of albuminuria, extent of renal tissue injury, and functional parameters. In addition, lupus-prone (NZB x NZW)F1 (NZB/NZW) mice were treated with anti-IL-17A and anti-interferon-gamma (anti-IFN gamma) antibodies, and their effects on the clinical course of lupus nephritis were assessed. Results. Characterization of renal IL-17A-producing and IFN gamma-producing T cells in MRL/lpr and NZB/NZW mice revealed low numbers of infiltrating CD3+IL-17A+ cells. Renal IL-17A was mainly produced by CD4/CD8 double-negative CD3+ T cells and CD4+ Th17 cells. In contrast, the number of renal CD3+IFN gamma+ cells continuously increased over time and largely consisted of typical CD4+ Th1 cells. IL-17A deficiency did not affect the morphologic or functional parameters in MRL/lpr mice with lupus nephritis, nor did IL-17A neutralization affect the clinical course of nephritis in NZB/NZW mice, but anti-IFN gamma+ treatment attenuated the severity of the disease. Conclusion. The Th17/IL-17A immune response plays no major role in the immunopathogenesis of lupus nephritis in MRL/lpr and NZB/NZW mice. Thus, the results of this study do not support the hypothesis that IL-17A targeting could be an intriguing new therapeutic approach for the management of proliferative lupus nephritis in SLE patients.
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Key words
murine lupus nephritis,immune response,th17/interleukin‐17a,th17/interleukin‐17a
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