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- Title
Function of the Th17/Interleukin-17A Immune Response in Murine Lupus Nephritis.
- Authors
Schmidt, Tilman; Paust, Hans‐Joachim; Krebs, Christian F.; Turner, Jan‐Eric; Kaffke, Anna; Bennstein, Sabrina B.; Koyro, Tobias; Peters, Anett; Velden, Joachim; Hünemörder, Stefanie; Haag, Friedrich; Steinmetz, Oliver M.; Mittrücker, Hans‐Willi; Stahl, Rolf A. K.; Panzer, Ulf
- 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 × NZW)F1 (NZB/NZW) mice were treated with anti-IL-17A and anti-interferon-γ (anti-IFNγ) antibodies, and their effects on the clinical course of lupus nephritis were assessed. Results Characterization of renal IL-17A-producing and IFNγ-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+IFNγ+ 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-IFNγ 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.
- Subjects
GERMANY; T cells; ACADEMIC medical centers; ANALYSIS of variance; ANIMAL experimentation; BIOPSY; ENZYME-linked immunosorbent assay; FLOW cytometry; IMMUNOHISTOCHEMISTRY; MICE; POLYMERASE chain reaction; RESEARCH funding; STATISTICS; SYSTEMIC lupus erythematosus; T-test (Statistics); LUPUS nephritis; DATA analysis; REVERSE transcriptase polymerase chain reaction; PHYSIOLOGY
- Publication
Arthritis & Rheumatology, 2015, Vol 67, Issue 2, p475
- ISSN
2326-5191
- Publication type
Article
- DOI
10.1002/art.38955