Liver Immunology: Relevance to HCV Infection, Malignancy and Transplantation
The liver is an immunologically ‘tolerant’ organ equipped with powerful immunoregulatory mechanisms to control immune activity against harmless dietary and commensal antigens from the gut while remaining poised to respond to infection or malignancy. Through collaborations with the National Liver Transplant Centre at St. Vincent's University Hospital, we are exploring these mechanisms in the context of transplantation, hepatitis C and cancer. We have described the unique immunological repertoire of the liver which is characterised by major populations of innate immune cells including macrophages, DCs, NK, iNKT, MAIT and gamma delta T cells, as well as classic CD4+ and CD8+ T lymphocytes. These populations contribute to tissue repair as well as defence, tumour surveillance and immunoregulation. We were amongst the first in the world to propose that under normal conditions, some of these populations differentiate from haematopoietic stem cells in healthy liver and that this process is significantly compromised in patients with colorectal metastases. We have also found an interesting population of CD141+ DCs in human liver which we think could be an important target for vaccines against hepatotrophic pathogens such as HCV.
Our most recent liver publications:
Liver immunology and its role in inflammation and homeostasis. Robinson MW, Harmon C, O’Farrelly C. Cellular & Molecular Immunology (2016) 13, 267–276; doi:10.1038/cmi.2016.3 http://www.ncbi.nlm.nih.gov/pubmed/27063467
Natural Killer Cells and Liver Transplantation: Orchestrators of Rejection or Tolerance? Harmon C, Sanchez-Fueyo A, O'Farrelly C, Houlihan DD. Am J Transplant. 2016 Mar;16(3):751-7. doi: 10.1111/ajt.13565. Epub 2015 Dec 21. Review. http://www.ncbi.nlm.nih.gov/pubmed/26690302
The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function. Conroy MJ, Fitzgerald V, Doyle SL, Channon S, Useckaite Z, Gilmartin N, O'Farrelly C, Ravi N, Reynolds JV, Lysaght J. J Leukoc Biol. 2016 Jun 30. pii: jlb.5AB1115-493RR. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/27365528
CCR1 antagonism attenuates T cell trafficking to omentum and liver in obesity-associated cancer. Conroy MJ, Galvin KC, Kavanagh ME, Mongan AM, Doyle SL, Gilmartin N, O'Farrelly C, Reynolds JV, Lysaght J. Immunol Cell Biol. 2016 Jul;94(6):531-7. doi: 10.1038/icb.2016.26. Epub 2016 Apr 5. PMID: 27046081 http://www.ncbi.nlm.nih.gov/pubmed/27046081
CD141+ myeloid dendritic cells are enriched in healthy human liver. (2013) Kelly A, Fahey R, Fletcher JM, Keogh C, Carroll AG, Siddachari R, Geoghegan J, Hegarty JE, Ryan J, O'Farrelly C. Journal of Hepatology. http://www.ncbi.nlm.nih.gov/pubmed/23968887
And check out the editorial as well:
Hepatic CD141+IFNλ+ DC subset: One against all? (2013) Claudia Wegscheid, Khalil Karimi, Gisa Tiegs. Journal of Hepatology. http://www.ncbi.nlm.nih.gov/pubmed/24140762