Evidence map›Paper›PMID 37063857›Full record

ArticleFrontiers in immunology2023

Uncovering a novel role of focal adhesion and interferon-gamma in cellular rejection of kidney allografts at single cell resolution.

Ahmad Halawi, Abdullah B El Kurdi, Katherine A Vernon, Zhabiz Solhjou, John Y Choi, Anis J Saad, Nour K Younis, Rania Elfekih, Mostafa Tawfeek Mohammed, Christa A Deban and 8 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.8field-weighted citation impact, top 17% of its field
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

5 citing papers in PubMed, 7 citations in OpenAlex.

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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 at 6 institutions in 4 countries.

Ahmad HalawiTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Abdullah B El KurdiDepartment of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Katherine A VernonQ32 Bio, Waltham, MA, United States.
Zhabiz SolhjouTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
John Y ChoiTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Anis J SaadTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Nour K YounisTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Rania ElfekihTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Mostafa Tawfeek MohammedTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Christa A DebanTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Astrid WeinsDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
Reza AbdiTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Leonardo V RiellaDepartment of Medicine, Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Sasha A De SerresTransplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada.
Paolo CravediTranslational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Anna GrekaThe Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States.
Pierre KhoueiryDepartment of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Jamil R AzziTransplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Harvard University · USBrigham and Women's Hospital · USAmerican University of Beirut · LBBroad Institute · USIcahn School of Medicine at Mount Sinai · USUniversité Laval · CA

Funding

The novel role of the immunoproteasome subunit LMP7 in allo-immunity and T cell exhaustionR01AI134842 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI AZZI, JAMIL · 2018 to 2022
$1.9M
NIAID NIH HHS R01 AI134842
6 · The paper itself

Abstract

Background: Kidney transplant recipients are currently treated with nonspecific immunosuppressants that cause severe systemic side effects. Current immunosuppressants were developed based on their effect on T-cell activation rather than the underlying mechanisms driving alloimmune responses. Thus, understanding the role of the intragraft microenvironment will help us identify more directed therapies with lower side effects. Methods: To understand the role of the alloimmune response and the intragraft microenvironment in cellular rejection progression, we conducted a Single nucleus RNA sequencing (snRNA-seq) on one human non-rejecting kidney allograft sample, one borderline sample, and T-cell mediated rejection (TCMR) sample (Banff IIa). We studied the differential gene expression and enriched pathways in different conditions, in addition to ligand-receptor (L-R) interactions. Results: Pathway analysis of T-cells in borderline sample showed enrichment for allograft rejection pathway, suggesting that the borderline sample reflects an early rejection. Hence, this allows for studying the early stages of cellular rejection. Moreover, we showed that focal adhesion (FA), IFNg pathways, and endomucin (EMCN) were significantly upregulated in endothelial cell clusters (ECs) of borderline compared to ECs TCMR. Furthermore, we found that pericytes in TCMR seem to favor endothelial permeability compared to borderline. Similarly, T-cells interaction with ECs in borderline differs from TCMR by involving DAMPS-TLRs interactions. Conclusion: Our data revealed novel roles of T-cells, ECs, and pericytes in cellular rejection progression, providing new clues on the pathophysiology of allograft rejection.

Indexed as

Kidney TransplantationAllograftsFocal AdhesionsGraft RejectionHumansImmunosuppressive AgentsInterferon-gammaKidneyImmunosuppressive AgentsInterferon-gammaalloimmunitycellular microenvironmentgraft rejectionkidney transplantationsingle-cell analysis

Identifiers

PMID37063857
PMCPMC10102512
OpenAlexW4362470174

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.