Evidence map›Paper›PMID 42012886›Full record

ArticleJCI insight2026

Low-density neutrophil heterogeneity and spleen tyrosine kinase as therapeutic targets in sepsis.

Heather L Teague, Lauren Knabe, Raquel S Da Cruz, Xianglan Yao, Kiana C Allen, Trenton Williams, Cumhur Y Demirkale, Merte Woldehanna, Ernest Evans, Amir Hobson and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Association of CD16Journal of inflammation research · 2026
    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

14 authors.

Heather L TeagueCritical Care Medicine and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
Lauren KnabeCritical Care Medicine and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
Raquel S Da CruzCritical Care Medicine and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
Xianglan YaoCritical Care Medicine and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
Kiana C AllenCritical Care Medicine and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
Trenton WilliamsCritical Care Medicine and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
Cumhur Y DemirkaleCritical Care Medicine Department, Clinical Center, NIH, Bethesda, Maryland, USA.
Merte WoldehannaAdvanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA.
Ernest EvansAdvanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA.
Amir HobsonAdvanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA.
Jared D WilkinsonAdvanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA.
Steven D NathanAdvanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA.
Christopher S KingAdvanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA.
Jeffrey R StrichCritical Care Medicine and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sepsis is a leading cause of death for which host-directed therapies are urgently needed. We performed high-dimensional flow cytometry, measurement of soluble biomarkers, and lipopolysaccharide (LPS) stimulation of neutrophils to characterize neutrophil heterogeneity and function in patients with sepsis. We observed that in patients with sepsis, low-density neutrophils (LDNs) are elevated and phenotypically diverse populations of innate immune cells with varying degrees of maturity and myeloperoxidase expression. Spleen tyrosine kinase (SYK) expression was found to be higher in whole blood neutrophils and LDNs of patients with sepsis compared with healthy donors. Importantly, SYK+ LDNs associated with increased levels of intracellular myeloperoxidase (MPO) and soluble biomarkers. Furthermore, SYK+ LDNs correlated with clinical outcomes of sepsis disease severity, including sequential organ failure assessment score, mechanical ventilation, and vasopressors. Functionally, the SYK inhibitor R406 suppressed changes in neutrophil features of activation from normal-density neutrophils and LDNs, including the SYK+ and SYK- neutrophil subsets, and MPO release from LDNs following LPS stimulation of sepsis neutrophils. Combined, these results establish LDNs as a heterogenous population of neutrophils that express high levels of SYK and support SYK inhibition as a potentially novel therapeutic target aimed at suppressing overactive neutrophils in sepsis.

Indexed as

NeutrophilsSepsisSyk KinaseAgedAminopyridinesBiomarkersFemaleFlow CytometryHumansLipopolysaccharidesMaleMiddle AgedMorpholinesOxazinesPeroxidasePyridinesAminopyridinesBiomarkersfostamatinibLipopolysaccharidesMorpholinesN4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineOxazinesPeroxidasePyridinesPyrimidinesSyk KinaseSYK protein, humanImmunologyInflammationNeutrophils

Identifiers

PMID42012886
PMCPMC13313530

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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.