Researchers identified a natural ‘brake’ within the innate immune system: the inhibitory receptor Siglec-E (SigE) and its human counterparts, Siglec-7 and Siglec-9. This receptor helps prevent overactivation of immune cells that drive rejection. When this brake is missing, inflammation worsens, leading to faster rejection in preclinical models. Importantly, transplant patients with higher levels of Siglec-7 and Siglec-9 showed better graft survival, highlighting this pathway as a promising target for new therapies.