Vγ6+γδT Cells Participate in Lupus Nephritis in MRL/Lpr Mice

Int J Rheum Dis. 2025 Jan;28(1):e70040. doi: 10.1111/1756-185X.70040.

Abstract

Background: γδT cells have been implicated in the pathogenesis of autoimmune diseases. The study aims to investigate the abundance of γδT cells in MRL/lpr mice.

Methods: MRL/lpr mice were used as lupus models, while C3H/HeJ mice served as normal controls. The abundance of γδT cells in different organs was examined by flow cytometry. Plasma double-stranded DNA antibody levels, blood urea nitrogen, creatinine, and urinary protein levels were measured. Renal histopathology was observed via H&E staining. The correlations between the abundance of γδT cells and lupus manifestations were analyzed.

Results: Compared with C3H/HeJ mice, the number of γδT cells and Vγ6+γδT cell subset in the peripheral blood of MRL/lpr mice was significantly reduced. However, in the kidney, the number of γδT cells and Vγ6+γδT cell subset was significantly increased. Additionally, the number of Vγ6+γδT cells in the kidney was positively correlated with the urinary protein level. The number of IFN-γ+Vγ6+γδT cells in the kidney was positively correlated with urinary protein level.

Conclusion: In MRL/lpr mice, it is likely that peripheral γδT cells, especially the Vγ6 subset, infiltrate the kidney and secrete IFN-γ, which contributes to the development of lupus nephritis.

Keywords: IFN‐γ; lupus nephritis; subsets; γδT cells.

MeSH terms

  • Animals
  • Antibodies, Antinuclear* / blood
  • Disease Models, Animal*
  • Female
  • Interferon-gamma* / blood
  • Interferon-gamma* / metabolism
  • Intraepithelial Lymphocytes / immunology
  • Intraepithelial Lymphocytes / metabolism
  • Kidney* / immunology
  • Kidney* / metabolism
  • Kidney* / pathology
  • Lupus Nephritis* / immunology
  • Lupus Nephritis* / pathology
  • Mice
  • Mice, Inbred C3H*
  • Mice, Inbred MRL lpr*
  • Proteinuria / immunology
  • Receptors, Antigen, T-Cell, gamma-delta* / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Interferon-gamma
  • Antibodies, Antinuclear
  • IFNG protein, mouse
  • anti-dsDNA autoantibody