Trem2 activation by renal tubular debris sustains Arg1+ macrophage survival and promotes tubular epithelial repair in renal ischemia–reperfusion injury

Arg1⁺ macrophages play a pivotal role in tubular regeneration and repair. The myeloid receptor triggering receptor expressed on myeloid cells 2 (Trem2) mediates the clearance of cellular debris by recognizing lipid components from injured cells.

This study aimed to investigate whether Trem2 not only facilitates the debris clearance activity of Arg1⁺ macrophages in renal tubules but also sustains their survival, thereby providing a potential therapeutic target for the prevention and treatment of RIRI. To this end, we established stable RAW264.7 cell lines with Trem2 knockdown using lentivirus-mediated shRNA, followed by IL-4–induced polarization. Tubular epithelial fragments were prepared from TCMK-1 cells subjected to hypoxia/reoxygenation (H/R) and subsequently co-cultured with macrophages.