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

• Verfasst von: Siegler, Benedikt Hermann [VerfasserIn]
• Verfasst von: Thon, Jan Niklas [VerfasserIn]
• Verfasst von: Altvater, Marc [VerfasserIn]
• Verfasst von: Schenz, Judith [VerfasserIn]
• Verfasst von: Larmann, Jan [VerfasserIn]
• Verfasst von: Weigand, Markus A. [VerfasserIn]
• Verfasst von: Weiterer, Sebastian [VerfasserIn]
• 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
• DOI: doi:10.1371/journal.pone.0293347
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CHOLECYSTECTOMY
• Sach-SW: GENES
• Sach-SW: RECEPTORS
• Sach-SW: SERUM INTERLEUKIN-6
• K10plus-PPN: 1879951517

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.