2. Academic Validation
  3. The inhibitory receptor Siglec-E controls antigen-presenting cell activation and T cell-mediated transplant rejection

The inhibitory receptor Siglec-E controls antigen-presenting cell activation and T cell-mediated transplant rejection

  • Sci Transl Med. 2025 May 7;17(797):eads2694. doi: 10.1126/scitranslmed.ads2694.
Thiago J Borges 1,  Karina Lima 1,  Rodrigo B Gassen 1,  Kaifeng Liu 1,  Yoshikazu Ganchiku 1,  Guilherme T Ribas 1,  Minxue Liao 1,  Joao I B Goncalves 1,  Isadora T Lape 1,  Ivy A Rosales 2,  Yunlong Zhao 3,  Enfu Hui 3,  Robert L Fairchild 4 5,  Christian LeGuern 1,  Cristina Bonorino 6,  Stuart K Calderwood 7,  Joren C Madsen 1 8,  Leonardo V Riella 1 9
Affiliations

Affiliations

  • 1 Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
  • 2 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • 3 Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • 4 Department of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH 44196, USA.
  • 5 Transplant Center, Cleveland Clinic, Cleveland, OH 44196, USA.
  • 6 Immunotherapy Laboratory - (LAIT) - Department of Basic Health Sciences of Federal University of Health Sciences of Porto Alegre, UFCSPA, Porto Alegre 90050-170, Brazil.
  • 7 Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  • 8 Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • 9 Nephrology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
PMID: 40333992 DOI: 10.1126/scitranslmed.ads2694
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.

Figures
Products