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BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1445638

Understanding Complex Chromatin Dynamics of Primary Human Neutrophils During PMA Induced NET Formation

Provisionally accepted
Brandi Atteberry Brandi Atteberry Benjamin Berman Benjamin Berman Terry Kelly Terry Kelly Justin Cayford Justin Cayford *
  • Volition America Inc., Austin, United States

The final, formatted version of the article will be published soon.

    Primary human neutrophils play a pivotal role in innate immunity, mainly through the formation of neutrophil extracellular traps (NETs) in a process known as NETosis. This cell-death pathway is crucial for combating infections but is also implicated in many inflammatory diseases such as sepsis, systemic lupus erythematosus, rheumatoid arthritis, and others.The study presented here investigates chromatin dynamics during NET formation by stimulating primary human neutrophils with phorbol 12-myristate 13-acetate (PMA). We adapt the ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) method to isolated neutrophils and characterize a time-dependent chromatin response.We find that chromatin accessibility patterns are consistent across individual donors and most chromatin changes occur within 30 minutes, with many continuing across the 90 minutes assessed in this study. Regulatory regions gaining accessibility are associated with activity of pathways that have been implicated in NOX-dependent NET formation.Our findings enhance the understanding of the chromatin changes underlying NET formation and also identify potential early-acting targets for modulating this process in inflammatory diseases.

    Keywords: NEtosis, Neutrophil, ATAC-seq, Chromatin, PMA, Sepsis, innate immune system NETosis regulation 11, Net formation

    Received: 07 Jun 2024; Accepted: 26 Sep 2024.

    Copyright: © 2024 Atteberry, Berman, Kelly and Cayford. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Justin Cayford, Volition America Inc., Austin, United States

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