Sci Transl Med. 2025 May 7;17(797):eads2694. Epub 2025 May 7
Press release: MGH/Harvard
Authors:
Borges TJ, Lima K, Gassen RB, Liu K, Ganchiku Y, Ribas GT, Liao M, Goncalves JIB, Lape IT, Rosales IA, Zhao Y, Hui E, Fairchild RL, LeGuern C, Bonorino C, Calderwood SK, Madsen JC, Riella LV.
Abstract:
After transplantation, inflammation and tissue injury release danger signals that activate myeloid cells, driving adaptive immune responses and acute rejection. Current immunosuppressants primarily target T cells but inadequately control innate immunity. Regulatory signals controlling innate responses in transplantation remain elusive. The sialic acid–binding immunoglobulin-like lectin-E (Siglec-E, or SigE) binds sialylated ligands to suppress inflammation. In mouse heart transplants, SigE is up-regulated in graft-infiltrating myeloid cells, including dendritic cells (DCs). SigE deficiency in recipients, but not donors, accelerates acute rejection by enhancing DC activation, nuclear factor κB (NF-κB) signaling, and tumor necrosis factor–α (TNF-α) production, thereby boosting alloreactive T cell responses. Conversely, SigE overexpression on DCs reduces activation by danger signals and their T cell allostimulatory capacity. The human homologs Siglecs-7 and -9 were up-regulated in rejecting allograft biopsies, and their higher expression correlated with improved allograft survival. Thus, SigE/7/9 is a crucial inhibitory receptor controlling antigen-presenting cell activation and T cell–mediated transplant rejection, offering therapeutic potential.