The inhibitory receptor Siglec-E controls antigen-presenting cell activation and T cell–mediated transplant rejection
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.
Authors
- Minxue Liao (ORCID: https://orcid.org/0009-0003-4739-5011)
- Thiago J. Borges (ORCID: https://orcid.org/0000-0002-6554-0169)
- Ivy A. Rosales (ORCID: https://orcid.org/0000-0003-0621-3202)
- Karina Lima (ORCID: https://orcid.org/0000-0003-2478-1182)
- Rodrigo Benedetti Gassen (ORCID: https://orcid.org/0000-0003-0513-1555)
- Kaifeng Liu (ORCID: https://orcid.org/0009-0003-0157-8349)
- João Ismael Budelon Gonçalves (ORCID: https://orcid.org/0000-0001-9294-0486)
- Yoshikazu Ganchiku (ORCID: https://orcid.org/0000-0001-7122-3066)
- Cristina Bonorino (ORCID: https://orcid.org/0000-0003-2755-3978)
- Robert L. Fairchild (ORCID: https://orcid.org/0000-0002-7107-5259)
- Christian LeGuern
- Guilherme T. Ribas (ORCID: https://orcid.org/0000-0002-9752-4411)
- Isadora T. Lape
- Leonardo V. Riella (ORCID: https://orcid.org/0000-0002-7636-3196)
- Joren C. Madsen (ORCID: https://orcid.org/0000-0003-2724-1333)
- Enfu Hui (ORCID: https://orcid.org/0000-0001-7876-2783)
- Yunlong Zhao (ORCID: https://orcid.org/0000-0002-7392-4824)
- Stuart K. Calderwood (ORCID: https://orcid.org/0000-0003-1708-1137)
Institutions
- Beth Israel Deaconess Medical Center (US)
- Cleveland Clinic (US)
- Universidade Federal de Ciências da Saúde de Porto Alegre (BR)
- Harvard University (US)
- University of California San Diego (US)
- Massachusetts General Hospital (US)
- Institute of Infection and Immunity (CA)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2025-05-07
- DOI
- https://doi.org/10.1126/scitranslmed.ads2694
- Citations
- 7
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 5.58