Macrophages are recognized as vital players in renal fibrosis, with a high degree of heterogeneity and plasticity, and the triggering receptor expressed on myeloid cell-2 (TREM-2) is highly expressed on macrophages and participates in the progression of tissue fibrosis. However, the mechanism by which TREM-2 mediates the progression of renal fibrosis is still unclear. Our study revealed that exosomes derived from TREM-2-deficient (TREM-2