| 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 |
| Authors: |
Siegler, Benedikt Hermann; Thon, Jan Niklas; Altvater, Marc; Schenz, Judith; Larmann, Jan; Weigand, Markus Alexander; Weiterer, Sebastian |
| Contributors: |
Reismann, Marc; B. Braun-Stiftung; Heidelberger Stiftung Chirurgie |
| Source: |
PLOS ONE ; volume 18, issue 10, page e0293347 ; ISSN 1932-6203 |
| Publisher Information: |
Public Library of Science (PLoS) |
| Publication Year: |
2023 |
| Collection: |
PLOS Publications (via CrossRef) |
| 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1371/journal.pone.0293347 |
| Availability: |
https://doi.org/10.1371/journal.pone.0293347; https://dx.plos.org/10.1371/journal.pone.0293347 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.E83B954E |
| Database: |
BASE |