Evidence map›Paper›PMID 34003794›Full record

ArticleJCI insight2021

Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT.

Elisa Zaghi, Michela Calvi, Simone Puccio, Gianmarco Spata, Sara Terzoli, Clelia Peano, Alessandra Roberto, Federica De Paoli, Jasper Jp van Beek, Jacopo Mariotti and 12 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
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  4. Article
  5. Fatty acid oxidation fuels natural killer cell responses against infection and cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  11. Persistence of KIRFrontiers in immunology · 2023
    Article
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  13. Review
  14. Article
  15. Article
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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

22 authors at 5 institutions in 2 countries.

Elisa ZaghiUnit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Michela CalviUnit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Simone PuccioLaboratory of Translational Immunology.
Gianmarco SpataUnit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Sara TerzoliUnit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Clelia PeanoInstitute of Genetic and Biomedical Research, UoS Milan, National Research Council, and Genomic Unit.
Alessandra RobertoLaboratory of Translational Immunology.
Federica De PaoliLaboratory of Translational Immunology.
Jasper Jp van BeekLaboratory of Translational Immunology.
Jacopo MariottiBone Marrow Transplant Unit, and.
Chiara De PhilippisBone Marrow Transplant Unit, and.
Barbara SarinaBone Marrow Transplant Unit, and.
Rossana MineriMolecular Biology Section, Clinical Investigation Laboratory, IRCCS Humanitas Research Hospital, Milan, Italy.
Stefania BramantiBone Marrow Transplant Unit, and.
Armando SantoroBone Marrow Transplant Unit, and.
Vu Thuy Khanh Le-TrillingInstitute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Mirko TrillingInstitute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Emanuela MarcenaroDepartment of Experimental Medicine, University of Genoa, Genoa, Italy.
Luca CastagnaBone Marrow Transplant Unit, and.
Clara Di VitoUnit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Enrico LugliLaboratory of Translational Immunology.
Domenico MavilioUnit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
National Marrow Donor Program · USIRCCS Humanitas Research Hospital · ITUniversity of Milan · ITNational Academies of Sciences, Engineering, and Medicine · USUniversity of Genoa · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Haploidentical hematopoietic stem cell transplantation (h-HSCT) represents an efficient curative approach for patients affected by hematologic malignancies in which the reduced intensity conditioning induces a state of immunologic tolerance between donor and recipient. However, opportunistic viral infections greatly affect h-HSCT clinical outcomes. NK cells are the first lymphocytes that recover after transplant and provide a prompt defense against human cytomegalovirus (HCMV) infection/reactivation. By undertaking a longitudinal single-cell computational profiling of multiparametric flow cytometry, we show that HCMV accelerates NK cell immune reconstitution together with the expansion of CD158b1b2jpos/NKG2Aneg/NKG2Cpos/NKp30lo NK cells. The frequency of this subset correlates with HCMV viremia, further increases in recipients experiencing multiple episodes of viral reactivations, and persists for months after the infection. The transcriptional profile of FACS-sorted CD158b1b2jpos NK cells confirmed the ability of HCMV to deregulate NKG2C, NKG2A, and NKp30 gene expression, thus inducing the expansion of NK cells with adaptive traits. These NK cells are characterized by the downmodulation of several gene pathways associated with cell migration, the cell cycle, and effector-functions, as well as by a state of metabolic/cellular exhaustion. This profile reflects the functional impairments of adaptive NK cells to produce IFN-γ, a phenomenon also due to the viral-induced expression of lymphocyte-activation gene 3 (LAG-3) and programmed cell death protein 1 (PD-1) checkpoint inhibitors.

Indexed as

AdultAgedCytomegalovirus InfectionsFemaleHematopoietic Stem Cell TransplantationHumansKiller Cells, NaturalMaleMiddle AgedRNA-SeqSingle-Cell AnalysisTranscriptomeYoung AdultBone marrow transplantationHematologyImmunologyInnate immunityNK cells

Identifiers

PMID34003794
PMCPMC8262468
OpenAlexW3161766742

What OpenQuestion holds

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Registered trials

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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.