Cytokine-induced chromatin accessibility in whole blood neutrophils links to sepsis transcriptional states
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By
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Justin Cayford
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Brandi Atteberry
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Akanksha Singh-Taylor
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Andrew Retter
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Benjamin P. Berman
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Theresa K. Kelly
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June 10, 2026
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Clinical Scorecard: Cytokine-Driven Changes in Chromatin Accessibility of Neutrophils in Whole Blood Correlate with Transcriptional Profiles in Sepsis
At a Glance
| Category | Detail |
| Condition | Sepsis and NET-associated inflammatory diseases |
| Key Mechanisms | Cytokine stimulation alters chromatin accessibility in neutrophils, influencing transcriptional profiles related to disease severity. |
| Target Population | Patients with sepsis and other NET-associated inflammatory diseases. |
| Care Setting | Clinical and research settings involving whole blood analysis. |
Key Highlights
- Neutrophils form NETs to trap pathogens, but excessive NET release can lead to organ dysfunction and increased mortality.
- Natural factors (NFs) induce distinct chromatin accessibility programs in neutrophils compared to PMA stimulation.
- Chromatin accessibility changes correlate with transcriptional states associated with sepsis severity.
- Cytokines such as TNF-α, GM-CSF, and IL-1β are involved in neutrophil activation and NET formation.
- The study provides a framework for linking cytokine-driven neutrophil regulation to inflammatory states.
Guideline-Based Recommendations
Diagnosis
- Assess chromatin accessibility changes in neutrophils as potential biomarkers for sepsis severity.
Management
- Consider the role of cytokines in neutrophil activation and NET formation when managing sepsis.
Monitoring & Follow-up
- Monitor neutrophil chromatin accessibility and transcriptional profiles in patients with sepsis.
Risks
- Excessive NET formation can lead to immunothrombosis and organ dysfunction.
Patient & Prescribing Data
Patients with sepsis and inflammatory diseases linked to NETs.
Understanding cytokine interactions may inform treatment strategies targeting neutrophil responses.
Clinical Best Practices
- Utilize whole blood for profiling neutrophil chromatin accessibility to reflect in vivo conditions.
- Incorporate assessment of inflammatory cytokines in the evaluation of sepsis.
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