ArticleCell death and differentiation2026
A neutrophil-intrinsic CKLF1-PKM2 axis drives glycolytic flux for de novo DAG synthesis and pro-inflammatory ROS production.
Article in Cell death and differentiation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reactive oxygen species (ROS) burst and subsequent recruitment to the ischemic brain characterize neutrophil activation in the hyperacute phase of ischemic stroke, yet the underlying metabolic drivers remain elusive. Here, we report that neutrophil-intrinsic chemokine-like factor 1 (CKLF1) acts as a key immunometabolic regulator following stroke. CKLF1 was rapidly upregulated in neutrophils within 6 h post-ischemia in both humans and mice. Mechanistically, CKLF1 bound directly to the tetrameric form of pyruvate kinase M2 (PKM2), enhancing glycolytic flux and diverting intermediates toward de novo diacylglycerol (DAG) synthesis. This rewiring promoted protein kinase C-dependent phosphorylation of p47‑phox and assembly of NADPH oxidase, driving ROS production that reinforced neutrophil recruitment and adhesion via αMβ2 integrin. Genetic deletion of neutrophil CKLF1 attenuated neutrophil recruitment and improved functional recovery. Leveraging this mechanism, we developed a neutrophil-targeted nanotherapeutic using engineered outer membrane vesicles from E. coli W3110 to deliver a stapled CKLF1-derived peptide (C19) that disrupts CKLF1-PKM2 binding. This intervention suppressed glycolysis-driven ROS, reduced neutrophil recruitment and αMβ2 expression, and provided robust neuroprotection. Our findings reveal a CKLF1-PKM2-DAG axis that directs metabolic reprogramming and neutrophil pathogenicity in stroke, offering a novel target for immunometabolic therapy.
Identifiers
42120940What OpenQuestion holds
Registered trials
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.