Palmitoylation of CD36 enhances lipid droplet accumulation and M2-like polarization in decidual macrophages at the maternal-fetal interface

Successful pregnancy relies on immune homeostasis at the maternal-fetal interface, where decidual macrophages (dMφ) play a crucial role in spiral artery remodelling, antigen presentation, and clearing apoptotic cells. Dysfunctions in dMφ have been linked to recurrent pregnancy loss (RPL), however, the underlying molecular mechanisms are not fully understood. In this study, we identified a novel subset of tissue-resident dMφ, through single-cell RNA sequencing, characterized by high expression of CD36 and predominant lipid metabolism, and significantly decreased in RPL patients. Our results demonstrate that trophoblasts promote lipid droplet accumulation and anti-inflammatory cytokine secretion in this subset of dMφ by regulating CD36 palmitoylation. Furthermore, we identified key palmitoyltransferases that function in this process and found that the palmitoylation of CD36 is crucial for maintaining immune tolerance and the M2-like phenotype of dMφ. Our findings highlight the significance of CD36 palmitoylation-mediated lipid metabolism in dMφ in maintaining decidua immune homeostasis and provide insights into the pathological mechanisms underlying RPL.