"Lipocalin-2 modulates recipients alloimmune responses to the murine kidney transplants." was published by A.M. Pfefferkorn , R. Fritsche-Guenther, A. Kusch, H. Schwelberger, S. Liu, R. Klopfleisch, Y. Li, R. Catar, S. Liu, F. Aigner, J. Pratschke, I.M. Sauer, and M.I. Ashraf in the December Issue of Frontiers in Immunology 2025.

This study investigated the mechanisms behind the renoprotective effects of recombinant Lipocalin-2 (rLcn2) in kidney transplantation (KTx). Lipocalin-2 is known as an early biomarker for acute kidney injury, delayed graft function, and transplant rejection. Using a mouse kidney transplant model, researchers examined how rLcn2 affects immune responses after transplantation.
Treatment with rLcn2 (Lcn2:Siderophore:Fe³⁺ complex) significantly reduced T-cell activation and frequency, particularly effector memory T cells and their cytotoxic (CD8⁺) and helper (CD4⁺) subsets, in graft tissue, lymphoid organs, and blood by postoperative day 7. In graft-infiltrating CD8⁺ T cells, rLcn2 also reduced cytotoxic activity, including lower degranulation capacity and decreased interferon-γ and perforin expression, as well as fewer NKG2D⁺ activated cytotoxic T cells. Effects on innate immune cells were limited and selective, affecting only some neutrophils, macrophages, and NK cell subsets.
Importantly, rLcn2 did not influence inflammation or tissue injury in syngeneic (non-alloimmune) transplants, indicating that its protective effect is primarily through modulation of adaptive immune responses, particularly T-cell activity.
Overall, the findings suggest that rLcn2 improves kidney graft outcomes by selectively suppressing alloimmune T-cell responses rather than altering non-immune injury pathways.