Neutrophils in patients with chronic coronary syndrome exhibit delayed spontaneous apoptosis and resistance to regulatory T cell-induced apoptosis – Brief Report

  1. Maike Schneider
  2. Camilla Skoglund
  3. Rosanna WS Chung
  4. Lena Jonasson

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Abstract

Background

Persistent inflammation is linked to poor outcomes in patients with chronic coronary syndrome (CCS). The inflammatory state in atherosclerotic disease has been associated with activation of neutrophils as well as with regulatory T cell (T reg ) deficiency. The role of T regs in the regulation of neutrophil survival has been postulated recently. Here, we investigated neutrophil apoptosis along with the potential impact of T regs on neutrophil apoptosis in patients with CCS, compared to healthy controls.

Methods

Twenty patients with CCS and 19 healthy controls were included. Neutrophil apoptosis was assessed after 5h culture with or without interleukin(IL-)10, TNF or LPS. Neutrophil phenotype was evaluated through flow cytometry analysis of surface receptors (CD66b and CXCR4) and ex vivo release of cytokines and granule proteins. The ability of T regs to induce neutrophil apoptosis was examined in autologous neutrophil-T reg co-cultures.

Results

Spontaneous neutrophil apoptosis was significantly delayed in patients compared to controls (10.3% vs. 19.2%, p=0.025). Also, neutrophils from patients overexpressed CD66b and CXCR4 and were more prone to release proinflammatory mediators. Notably, T regs induced neutrophil apoptosis in healthy subjects, but not in patients, indicating a loss of T reg -mediated regulation in the latter. There was no evidence that IL-10 had any influence on neutrophil apoptosis. However, cell-to-cell contact was found essential for T reg -induced neutrophil apoptosis.

Conclusions

Patients with CCS display delayed neutrophil apoptosis and a pro-inflammatory neutrophil phenotype that is resistant to T reg -mediated apoptosis. Neutrophil dysfunction may contribute to persistent inflammation in patients with CCS, and as such constitute a novel therapeutic target.

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  1. PREreview

    This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/22958508.

    The empirical investigation into delayed spontaneous neutrophil apoptosis and the corresponding phenotypic resistance to regulatory T cell-mediated clearance in chronic coronary syndrome offers highly critical clinical insights. Characterizing these altered cell-death lifecycles bridges a major gap between persistent vascular inflammation and targeted cellular tracking.

    However, from a structural biochemistry perspective, the absolute focus on downstream apoptotic markers requires a tighter validation loop regarding the upstream mitochondrial membrane potential configurations. The authors should explicitly define the local microenvironmental signaling boundaries or specific cytokine configurations that suppress the standard apoptotic pathways in these specific patient cohorts. Bypassing these baseline kinetic parameters introduces substantial noise into the tracking of chronic inflammatory cascades.

    Additionally, investigating how these resistant neutrophil phenotypes alter local endothelial cell dynamics during spatial transmigration would provide a stronger validation benchmark. This technical adjustment strengthens the manuscript's predictive utility for independent investigators developing macromolecular targeted therapeutic interventions without relying on capital-intensive institutional screening systems.

    Competing interests

    The author declares that they have no competing interests.

    Use of Artificial Intelligence (AI)

    The author declares that they did not use generative AI to come up with new ideas for their review.

  2. Version published to 10.64898/2026.01.22.701200 on bioRxiv