Human Hepatic CD56bright NK Cells Display a Tissue-Resident Transcriptional Profile and Enhanced Ability to Kill Allogenic CD8+ T Cells
Liver-resident CD56brightCD16- natural killer (NK) cells are enriched in the human liver and are phenotypically distinct from their blood counterparts. Although these cells are capable of rapid cytotoxic effector activity, their functional role remains unclear. We hypothesise that they may contribut...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.921212/full |
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| author | Gráinne Jameson Cathal Harmon Rhyla Mae Santiago Diarmaid D. Houlihan Tom K. Gallagher Lydia Lynch Mark W. Robinson Cliona O’Farrelly Cliona O’Farrelly |
| author_facet | Gráinne Jameson Cathal Harmon Rhyla Mae Santiago Diarmaid D. Houlihan Tom K. Gallagher Lydia Lynch Mark W. Robinson Cliona O’Farrelly Cliona O’Farrelly |
| author_sort | Gráinne Jameson |
| collection | DOAJ |
| description | Liver-resident CD56brightCD16- natural killer (NK) cells are enriched in the human liver and are phenotypically distinct from their blood counterparts. Although these cells are capable of rapid cytotoxic effector activity, their functional role remains unclear. We hypothesise that they may contribute to immune tolerance in the liver during transplantation. RNA sequencing was carried out on FACS sorted NK cell subpopulations from liver perfusates (n=5) and healthy blood controls (n=5). Liver-resident CD56brightCD16+/- NK cells upregulate genes associated with tissue residency. They also upregulate expression of CD160 and LY9, both of which encode immune receptors capable of activating NK cells. Co-expression of CD160 and Ly9 on liver-resident NK cells was validated using flow cytometry. Hepatic NK cell cytotoxicity against allogenic T cells was tested using an in vitro co-culture system of liver perfusate-derived NK cells and blood T cells (n=10-13). In co-culture experiments, hepatic NK cells but not blood NK cells induced significant allogenic T cell death (p=0.0306). Allogenic CD8+ T cells were more susceptible to hepatic NK cytotoxicity than CD4+ T cells (p<0.0001). Stimulation of hepatic CD56bright NK cells with an anti-CD160 agonist mAb enhanced this cytotoxic response (p=0.0382). Our results highlight a role for donor liver NK cells in regulating allogenic CD8+ T cell activation, which may be important in controlling recipient CD8+ T cell-mediated rejection post liver-transplant. |
| first_indexed | 2024-12-11T18:41:04Z |
| format | Article |
| id | doaj.art-d85721e6345648c9a722293ac2094e71 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T18:41:04Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d85721e6345648c9a722293ac2094e712022-12-22T00:54:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.921212921212Human Hepatic CD56bright NK Cells Display a Tissue-Resident Transcriptional Profile and Enhanced Ability to Kill Allogenic CD8+ T CellsGráinne Jameson0Cathal Harmon1Rhyla Mae Santiago2Diarmaid D. Houlihan3Tom K. Gallagher4Lydia Lynch5Mark W. Robinson6Cliona O’Farrelly7Cliona O’Farrelly8School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, IrelandBrigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Biology, Kathleen Lonsdale Institute of Human Health Research, Maynooth University, Maynooth, IrelandLiver Unit, St. Vincent’s University Hospital, Dublin, IrelandHepatopancreaticobiliary Group, St. Vincent’s University Hospital, Dublin, IrelandBrigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Biology, Kathleen Lonsdale Institute of Human Health Research, Maynooth University, Maynooth, IrelandSchool of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandLiver-resident CD56brightCD16- natural killer (NK) cells are enriched in the human liver and are phenotypically distinct from their blood counterparts. Although these cells are capable of rapid cytotoxic effector activity, their functional role remains unclear. We hypothesise that they may contribute to immune tolerance in the liver during transplantation. RNA sequencing was carried out on FACS sorted NK cell subpopulations from liver perfusates (n=5) and healthy blood controls (n=5). Liver-resident CD56brightCD16+/- NK cells upregulate genes associated with tissue residency. They also upregulate expression of CD160 and LY9, both of which encode immune receptors capable of activating NK cells. Co-expression of CD160 and Ly9 on liver-resident NK cells was validated using flow cytometry. Hepatic NK cell cytotoxicity against allogenic T cells was tested using an in vitro co-culture system of liver perfusate-derived NK cells and blood T cells (n=10-13). In co-culture experiments, hepatic NK cells but not blood NK cells induced significant allogenic T cell death (p=0.0306). Allogenic CD8+ T cells were more susceptible to hepatic NK cytotoxicity than CD4+ T cells (p<0.0001). Stimulation of hepatic CD56bright NK cells with an anti-CD160 agonist mAb enhanced this cytotoxic response (p=0.0382). Our results highlight a role for donor liver NK cells in regulating allogenic CD8+ T cell activation, which may be important in controlling recipient CD8+ T cell-mediated rejection post liver-transplant.https://www.frontiersin.org/articles/10.3389/fimmu.2022.921212/fullNK cellresidentCD8+ T celllivertransplanttolerance |
| spellingShingle | Gráinne Jameson Cathal Harmon Rhyla Mae Santiago Diarmaid D. Houlihan Tom K. Gallagher Lydia Lynch Mark W. Robinson Cliona O’Farrelly Cliona O’Farrelly Human Hepatic CD56bright NK Cells Display a Tissue-Resident Transcriptional Profile and Enhanced Ability to Kill Allogenic CD8+ T Cells Frontiers in Immunology NK cell resident CD8+ T cell liver transplant tolerance |
| title | Human Hepatic CD56bright NK Cells Display a Tissue-Resident Transcriptional Profile and Enhanced Ability to Kill Allogenic CD8+ T Cells |
| title_full | Human Hepatic CD56bright NK Cells Display a Tissue-Resident Transcriptional Profile and Enhanced Ability to Kill Allogenic CD8+ T Cells |
| title_fullStr | Human Hepatic CD56bright NK Cells Display a Tissue-Resident Transcriptional Profile and Enhanced Ability to Kill Allogenic CD8+ T Cells |
| title_full_unstemmed | Human Hepatic CD56bright NK Cells Display a Tissue-Resident Transcriptional Profile and Enhanced Ability to Kill Allogenic CD8+ T Cells |
| title_short | Human Hepatic CD56bright NK Cells Display a Tissue-Resident Transcriptional Profile and Enhanced Ability to Kill Allogenic CD8+ T Cells |
| title_sort | human hepatic cd56bright nk cells display a tissue resident transcriptional profile and enhanced ability to kill allogenic cd8 t cells |
| topic | NK cell resident CD8+ T cell liver transplant tolerance |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.921212/full |
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