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Abdominal surgery induces long-lasting changes in expression and binding of CTCF with impact on Major Histocompatibility Complex II transcription in circulating human monocytes

PloS one, 2023-10, Vol.18 (10), p.e0293347-e0293347 [Peer Reviewed Journal]

2023 Siegler et al 2023 Siegler et al ;ISSN: 1932-6203 ;EISSN: 1932-6203 ;DOI: 10.1371/journal.pone.0293347 ;PMID: 37878653

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  • Title:
    Abdominal surgery induces long-lasting changes in expression and binding of CTCF with impact on Major Histocompatibility Complex II transcription in circulating human monocytes
  • Author: Siegler, Benedikt Hermann ; Thon, Jan Niklas ; Altvater, Marc ; Schenz, Judith ; Larmann, Jan ; Weigand, Markus Alexander ; Weiterer, Sebastian
  • Reismann, Marc
  • Subjects: Biology and Life Sciences ; Medicine and Health Sciences
  • Is Part Of: PloS one, 2023-10, Vol.18 (10), p.e0293347-e0293347
  • Description: Background Postoperative immunosuppression has been recognized as an important driver of surgery-related morbidity and mortality. It is characterized by lymphocyte depression and impaired monocyte capability to present foreign antigens to T-cells via Major Histocompatibility Complex, Class II (MHC-II) molecules. In patients with postoperative abdominal sepsis, we previously detected a persisting differential binding of the CCCTC-Binding Factor (CTCF), a superordinate regulator of transcription, inside the MHC-II region with specific impact on human leucocyte antigen (HLA) gene expression. In this prospective exploratory study, we investigated to which extent major surgery affects the MHC-II region of circulating CD14 + -monocytes. Results In non-immunocompromised patients undergoing elective major abdominal surgery, a postoperative loss of monocyte HLA-DR surface receptor density was accompanied by a decline in the transcription levels of the classical MHC-II genes HLA-DRA , HLA-DRB1 , HLA-DPA1 and HLA-DPB1 . The surgical event decreased the expression of the transcriptional MHC-II regulators CIITA and CTCF and led to a lower CTCF enrichment at an intergenic sequence within the HLA-DR subregion. During the observation period, we found a slow and only incomplete restoration of monocyte HLA-DR surface receptor density as well as a partial recovery of CIITA , HLA-DRA and HLA-DRB1 expression. In contrast, transcription of HLA-DPA1 , HLA-DPB1 , CTCF and binding of CTCF within the MHC-II remained altered. Conclusion In circulating monocytes, major surgery does not globally affect MHC-II transcription but rather induces specific changes in the expression of selected HLA genes, followed by differential recovery patterns and accompanied by a prolonged reduction of CTCF expression and binding within the MHC-II region. Our results hint toward a long-lasting impact of a major surgical intervention on monocyte functionality, possibly mediated by epigenetic changes that endure the life span of the individual cell.
  • Publisher: San Francisco, CA USA: Public Library of Science
  • Language: English
  • Identifier: ISSN: 1932-6203
    EISSN: 1932-6203
    DOI: 10.1371/journal.pone.0293347
    PMID: 37878653
  • Source: GFMER Free Medical Journals
    PubMed Central
    Public Library of Science (PLoS)
    ProQuest Central
    DOAJ Directory of Open Access Journals

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