Evidence map›Paper›PMID 40333992›Full record

ArticleScience translational medicine2025

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

Thiago J Borges, Karina Lima, Rodrigo B Gassen, Kaifeng Liu, Yoshikazu Ganchiku, Guilherme T Ribas, Minxue Liao, Joao I B Goncalves, Isadora T Lape, Ivy A Rosales and 8 more

Abstract read
In one paragraph

Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Observational
  4. Article
  5. Best practices in mouse models of skin transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026
    Review
  6. Article
  7. Review
  8. Review
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Thiago J BorgesCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.ORCID 0000-0002-6554-0169
Karina LimaCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.ORCID 0000-0003-2478-1182
Rodrigo B GassenCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.ORCID 0000-0003-0513-1555
Kaifeng LiuCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Yoshikazu GanchikuCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.ORCID 0000-0001-7122-3066
Guilherme T RibasCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.ORCID 0000-0002-9752-4411
Minxue LiaoCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.ORCID 0009-0003-4739-5011
Joao I B GoncalvesCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Isadora T LapeCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Ivy A RosalesDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0003-0621-3202
Yunlong ZhaoDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-7392-4824
Enfu HuiDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-7876-2783
Robert L FairchildDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH 44196, USA.ORCID 0000-0002-7107-5259
Christian LeGuernCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.ORCID 0009-0004-1137-7310
Cristina BonorinoImmunotherapy Laboratory - (LAIT) - Department of Basic Health Sciences of Federal University of Health Sciences of Porto Alegre, UFCSPA, Porto Alegre 90050-170, Brazil.ORCID 0000-0003-2755-3978
Stuart K CalderwoodDepartment of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Joren C MadsenCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.ORCID 0000-0003-2724-1333
Leonardo V RiellaCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.ORCID 0000-0002-7636-3196

Funding

Project 2: The New Era of Cellular Therapies For Lung Transplant ToleranceU19AI174967 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Joren C Madsen · 2023 to 2026
$18.8M
Using trained immunity-inhibiting nanobiologics to achieve tolerance of heart allografts in non-human primatesP01AI168258 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Zahi A. Fayad, Joren C Madsen · 2023 to 2026
$14.7M
Project 3: Enhanced Costimulation Blockade to Achieve Clinically Relevant Heart Allograft ToleranceP01HL158504 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI PIERSON, RICHARD N · 2021 to 2025
$12.1M
Regulation of PD-L1/PD-1 immune checkpoints by cis-interactionsR37CA239072 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HUI, ENFU · 2019 to 2025
$2.5M
Role of Siglec-E in Regulating AlloimmunityR01AI143887 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RIELLA, LEONARDO V. · 2019 to 2023
$2.1M
NCI NIH HHS R37 CA239072NHLBI NIH HHS P01 HL158504NIAID NIH HHS P01 AI168258NIAID NIH HHS R01 AI143887NIAID NIH HHS U19 AI174967
6 · The paper itself

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.

Indexed as

Antigen-Presenting CellsGraft RejectionLymphocyte ActivationSialic Acid Binding Immunoglobulin-like LectinsT-LymphocytesAnimalsDendritic CellsHeart TransplantationHumansMiceSignal TransductionSialic Acid Binding Immunoglobulin-like Lectins

Identifiers

PMID40333992
PMCPMC12135932

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.