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Verfasst von:Siegler, Benedikt Hermann [VerfasserIn]   i
 Thon, Jan Niklas [VerfasserIn]   i
 Altvater, Marc [VerfasserIn]   i
 Schenz, Judith [VerfasserIn]   i
 Larmann, Jan [VerfasserIn]   i
 Weigand, Markus A. [VerfasserIn]   i
 Weiterer, Sebastian [VerfasserIn]   i
Titel:Abdominal surgery induces long-lasting changes in expression and binding of CTCF with impact on Major Histocompatibility Complex II transcription in circulating human monocytes
Verf.angabe:Benedikt Hermann Siegler, Jan Niklas Thon, Marc Altvater, Judith Schenz, Jan Larmann, Markus Alexander Weigand, Sebastian Weiterer
E-Jahr:2023
Jahr:October 25, 2023
Umfang:16 S.
Illustrationen:Diagramme
Fussnoten:Gesehen am 05.02.2024
Titel Quelle:Enthalten in: PLOS ONE
Ort Quelle:San Francisco, California, US : PLOS, 2006
Jahr Quelle:2023
Band/Heft Quelle:18(2023), 10, Artikel-ID e0293347, Seite 1-16
ISSN Quelle:1932-6203
Abstract:BackgroundPostoperative 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.ResultsIn 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.ConclusionIn 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.
DOI:doi:10.1371/journal.pone.0293347
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kostenfrei: Volltext: https://doi.org/10.1371/journal.pone.0293347
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 DOI: https://doi.org/10.1371/journal.pone.0293347
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:CHOLECYSTECTOMY
 GENES
 RECEPTORS
 SERUM INTERLEUKIN-6
K10plus-PPN:1879951517
Verknüpfungen:→ Zeitschrift

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