Function of the Th17/Interleukin‐17A Immune Response in Murine Lupus Nephritis

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‐Faslpr/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.