Low-Dose rIL-15 Protects from Nephrotoxic Serum Nephritis via CD8+ T Cells

Cells. 2022 Nov 18;11(22):3656. doi: 10.3390/cells11223656.


Rapid progressive glomerulonephritis (GN) often leads to end-stage kidney disease, driving the need for renal replacement therapy and posing a global health burden. Low-dose cytokine-based immunotherapies provide a new strategy to treat GN. IL-15 is a strong candidate for the therapy of immune-mediated kidney disease since it has proven to be tubular-protective before. Therefore, we set out to test the potential of low-dose rIL-15 treatment in a mouse model of nephrotoxic serum nephritis (NTS), mimicking immune complex-driven GN in humans. A single low-dose treatment with rIL-15 ameliorated NTS, reflected by reduced albuminuria, less tissue scarring, fewer myeloid cells in the kidney, and improved tubular epithelial cell survival. In addition, CD8+ T cells, a primary target of IL-15, showed altered gene expression and function corresponding with less cytotoxicity mediated by rIL-15. With the use of transgenic knock-out mice, antibody depletion, and adoptive cell transfer studies, we here show that the beneficial effects of rIL-15 treatment in NTS depended on CD8+ T cells, suggesting a pivotal role for them in the underlying mechanism. Our findings add to existing evidence of the association of IL-15 with kidney health and imply a potential for low-dose rIL-15 immunotherapies in GN.

Keywords: glomerulonephritis; interleukin-15; renal tubular epithelial cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Glomerulonephritis* / drug therapy
  • Humans
  • Interleukin-15 / metabolism
  • Interleukin-15 / pharmacology
  • Kidney / metabolism
  • Mice
  • Mice, Knockout
  • Nephritis*


  • Interleukin-15

Grant support

This work was funded by the Austrian Science Fund (DK-MOLIN-FWF W1241 to K.E.). Open Access Funding by the Austrian Science Fund (FWF).