Inflammatory Monocytes Are Rapidly Recruited to the Post-Ischaemic Liver in Patients Undergoing Liver Transplantation and Cytokines Associated with Their Activation Correlate with Graft Outcomes
Liver ischaemia–reperfusion (IR) injury remains a major cause of morbidity and mortality following liver transplantation and resection. CD4+ T cells have been shown to play a key role in murine models; however, there is currently a lack of data that support their role in human patients. <i>Met...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/47/1/49 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588758093922304 |
|---|---|
| author | Francis P. Robertson Antonia O. Cuff Victoria Male Graham P. Wright Laura J. Pallett Barry J. Fuller Brian R. Davidson |
| author_facet | Francis P. Robertson Antonia O. Cuff Victoria Male Graham P. Wright Laura J. Pallett Barry J. Fuller Brian R. Davidson |
| author_sort | Francis P. Robertson |
| collection | DOAJ |
| description | Liver ischaemia–reperfusion (IR) injury remains a major cause of morbidity and mortality following liver transplantation and resection. CD4+ T cells have been shown to play a key role in murine models; however, there is currently a lack of data that support their role in human patients. <i>Methods:</i> Data on clinical outcomes and complications were documented prospectively in 28 patients undergoing first elective liver transplant surgery. Peripheral blood samples were collected at baseline (pre-op), 2 h post graft reperfusion, immediately post-op, and 24 h post-op. A post-reperfusion biopsy was analysed in all patients, and in five patients, a donor liver biopsy was available pre-implantation. Circulating cytokines were measured, and T cells were analysed for activation markers and cytokine production. <i>Results:</i> Circulating levels of cytokines associated with innate immune cell recruitment and activation were significantly elevated in the peri-transplant period. High circulating IL-10 levels corresponded with the development of graft-specific complications. The proportion of CD4+ T cells in the peripheral circulation fell throughout the peri-operative period, suggesting CD4+ T cell recruitment to the graft. Although TNFα was the predominant cytokine produced by CD4+ T cells in the intrahepatic environment, the production of IFNγ was significantly upregulated by circulating CD4+ T cells. Furthermore, we demonstrated clear recruitment of inflammatory monocytes in the peri-operative period. In donor-and-recipient pairs with a mismatch at the HLA-A2 or A3 allele, we demonstrated that inflammatory monocytes in the liver are recipient-derived. <i>Discussion:</i> This is the first study to our knowledge that tracks early immune cell responses in humans undergoing liver transplantation. The recruitment of inflammatory monocytes from the recipient and their cytokine release is associated with liver-specific complications. Inflammatory monocytes would be an attractive target to ameliorate ischaemia–reperfusion injury. |
| format | Article |
| id | doaj-art-3e92a95f75df4bf897c9904d6ca0bd1a |
| institution | Kabale University |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj-art-3e92a95f75df4bf897c9904d6ca0bd1a2025-01-24T13:27:32ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-01-014714910.3390/cimb47010049Inflammatory Monocytes Are Rapidly Recruited to the Post-Ischaemic Liver in Patients Undergoing Liver Transplantation and Cytokines Associated with Their Activation Correlate with Graft OutcomesFrancis P. Robertson0Antonia O. Cuff1Victoria Male2Graham P. Wright3Laura J. Pallett4Barry J. Fuller5Brian R. Davidson6Division of Interventional and Surgical Science, Royal Free Campus, University College London, London NW3 2QG, UKDivision of Biomedical Sciences, Warwick Medical School, Gibbet Hill Campus, University of Warwick, Coventry CV4 7AL, UKDepartment of Metabolism, Digestion and Reproduction, Chelsea and Westminster Hospital Campus, Imperial College London, London W12 0NN, UKSchool of Applied Science, Edinburgh Napier University, Edinburgh EH11 4BN, UKInstitute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PP, UKDivision of Interventional and Surgical Science, Royal Free Campus, University College London, London NW3 2QG, UKDivision of Interventional and Surgical Science, Royal Free Campus, University College London, London NW3 2QG, UKLiver ischaemia–reperfusion (IR) injury remains a major cause of morbidity and mortality following liver transplantation and resection. CD4+ T cells have been shown to play a key role in murine models; however, there is currently a lack of data that support their role in human patients. <i>Methods:</i> Data on clinical outcomes and complications were documented prospectively in 28 patients undergoing first elective liver transplant surgery. Peripheral blood samples were collected at baseline (pre-op), 2 h post graft reperfusion, immediately post-op, and 24 h post-op. A post-reperfusion biopsy was analysed in all patients, and in five patients, a donor liver biopsy was available pre-implantation. Circulating cytokines were measured, and T cells were analysed for activation markers and cytokine production. <i>Results:</i> Circulating levels of cytokines associated with innate immune cell recruitment and activation were significantly elevated in the peri-transplant period. High circulating IL-10 levels corresponded with the development of graft-specific complications. The proportion of CD4+ T cells in the peripheral circulation fell throughout the peri-operative period, suggesting CD4+ T cell recruitment to the graft. Although TNFα was the predominant cytokine produced by CD4+ T cells in the intrahepatic environment, the production of IFNγ was significantly upregulated by circulating CD4+ T cells. Furthermore, we demonstrated clear recruitment of inflammatory monocytes in the peri-operative period. In donor-and-recipient pairs with a mismatch at the HLA-A2 or A3 allele, we demonstrated that inflammatory monocytes in the liver are recipient-derived. <i>Discussion:</i> This is the first study to our knowledge that tracks early immune cell responses in humans undergoing liver transplantation. The recruitment of inflammatory monocytes from the recipient and their cytokine release is associated with liver-specific complications. Inflammatory monocytes would be an attractive target to ameliorate ischaemia–reperfusion injury.https://www.mdpi.com/1467-3045/47/1/49liver transplantationischaemia–reperfusion injuryCD4+ T cellsinflammatory monocytes |
| spellingShingle | Francis P. Robertson Antonia O. Cuff Victoria Male Graham P. Wright Laura J. Pallett Barry J. Fuller Brian R. Davidson Inflammatory Monocytes Are Rapidly Recruited to the Post-Ischaemic Liver in Patients Undergoing Liver Transplantation and Cytokines Associated with Their Activation Correlate with Graft Outcomes Current Issues in Molecular Biology liver transplantation ischaemia–reperfusion injury CD4+ T cells inflammatory monocytes |
| title | Inflammatory Monocytes Are Rapidly Recruited to the Post-Ischaemic Liver in Patients Undergoing Liver Transplantation and Cytokines Associated with Their Activation Correlate with Graft Outcomes |
| title_full | Inflammatory Monocytes Are Rapidly Recruited to the Post-Ischaemic Liver in Patients Undergoing Liver Transplantation and Cytokines Associated with Their Activation Correlate with Graft Outcomes |
| title_fullStr | Inflammatory Monocytes Are Rapidly Recruited to the Post-Ischaemic Liver in Patients Undergoing Liver Transplantation and Cytokines Associated with Their Activation Correlate with Graft Outcomes |
| title_full_unstemmed | Inflammatory Monocytes Are Rapidly Recruited to the Post-Ischaemic Liver in Patients Undergoing Liver Transplantation and Cytokines Associated with Their Activation Correlate with Graft Outcomes |
| title_short | Inflammatory Monocytes Are Rapidly Recruited to the Post-Ischaemic Liver in Patients Undergoing Liver Transplantation and Cytokines Associated with Their Activation Correlate with Graft Outcomes |
| title_sort | inflammatory monocytes are rapidly recruited to the post ischaemic liver in patients undergoing liver transplantation and cytokines associated with their activation correlate with graft outcomes |
| topic | liver transplantation ischaemia–reperfusion injury CD4+ T cells inflammatory monocytes |
| url | https://www.mdpi.com/1467-3045/47/1/49 |
| work_keys_str_mv | AT francisprobertson inflammatorymonocytesarerapidlyrecruitedtothepostischaemicliverinpatientsundergoinglivertransplantationandcytokinesassociatedwiththeiractivationcorrelatewithgraftoutcomes AT antoniaocuff inflammatorymonocytesarerapidlyrecruitedtothepostischaemicliverinpatientsundergoinglivertransplantationandcytokinesassociatedwiththeiractivationcorrelatewithgraftoutcomes AT victoriamale inflammatorymonocytesarerapidlyrecruitedtothepostischaemicliverinpatientsundergoinglivertransplantationandcytokinesassociatedwiththeiractivationcorrelatewithgraftoutcomes AT grahampwright inflammatorymonocytesarerapidlyrecruitedtothepostischaemicliverinpatientsundergoinglivertransplantationandcytokinesassociatedwiththeiractivationcorrelatewithgraftoutcomes AT laurajpallett inflammatorymonocytesarerapidlyrecruitedtothepostischaemicliverinpatientsundergoinglivertransplantationandcytokinesassociatedwiththeiractivationcorrelatewithgraftoutcomes AT barryjfuller inflammatorymonocytesarerapidlyrecruitedtothepostischaemicliverinpatientsundergoinglivertransplantationandcytokinesassociatedwiththeiractivationcorrelatewithgraftoutcomes AT brianrdavidson inflammatorymonocytesarerapidlyrecruitedtothepostischaemicliverinpatientsundergoinglivertransplantationandcytokinesassociatedwiththeiractivationcorrelatewithgraftoutcomes |