Strategies to induce natural killer cell tolerance in xenotransplantation
Eliminating major xenoantigens in pig cells has drastically reduced human antibody-mediated hyperacute xenograft rejection (HXR). Despite these advancements, acute xenograft rejection (AXR) remains one of the major obstacles to clinical xenotransplantation, mediated by innate immune cells, including...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.941880/full |
| _version_ | 1817999072656621568 |
|---|---|
| author | Kevin J. Lopez Arthur A. Cross-Najafi Kristine Farag Benjamin Obando Deepthi Thadasina Abdulkadir Isidan Yujin Park Wenjun Zhang Burcin Ekser Ping Li |
| author_facet | Kevin J. Lopez Arthur A. Cross-Najafi Kristine Farag Benjamin Obando Deepthi Thadasina Abdulkadir Isidan Yujin Park Wenjun Zhang Burcin Ekser Ping Li |
| author_sort | Kevin J. Lopez |
| collection | DOAJ |
| description | Eliminating major xenoantigens in pig cells has drastically reduced human antibody-mediated hyperacute xenograft rejection (HXR). Despite these advancements, acute xenograft rejection (AXR) remains one of the major obstacles to clinical xenotransplantation, mediated by innate immune cells, including macrophages, neutrophils, and natural killer (NK) cells. NK cells play an ‘effector’ role by releasing cytotoxicity granules against xenogeneic cells and an ‘affecter’ role on other immune cells through cytokine secretion. We highlight the key receptor-ligand interactions that determine the NK cell response to target cells, focusing on the regulation of NK cell activating receptor (NKG2D, DNAM1) and inhibitory receptor (KIR2DL1-4, NKG2A, and LIR-1) signaling pathways. Inhibition of NK cell activity may protect xenografts from cytotoxicity. Recent successful approaches to reducing NK cell-mediated HXR and AXR are reviewed, including genetic modifications of porcine xenografts aimed at improving pig-to-human compatibility. Future directions to promote xenograft acceptance are discussed, including NK cell tolerance in pregnancy and NK cell evasion in viral infection. |
| first_indexed | 2024-04-14T03:01:52Z |
| format | Article |
| id | doaj.art-c3af84d9af5e4799b616044637c49274 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T03:01:52Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c3af84d9af5e4799b616044637c492742022-12-22T02:15:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.941880941880Strategies to induce natural killer cell tolerance in xenotransplantationKevin J. LopezArthur A. Cross-NajafiKristine FaragBenjamin ObandoDeepthi ThadasinaAbdulkadir IsidanYujin ParkWenjun ZhangBurcin EkserPing LiEliminating major xenoantigens in pig cells has drastically reduced human antibody-mediated hyperacute xenograft rejection (HXR). Despite these advancements, acute xenograft rejection (AXR) remains one of the major obstacles to clinical xenotransplantation, mediated by innate immune cells, including macrophages, neutrophils, and natural killer (NK) cells. NK cells play an ‘effector’ role by releasing cytotoxicity granules against xenogeneic cells and an ‘affecter’ role on other immune cells through cytokine secretion. We highlight the key receptor-ligand interactions that determine the NK cell response to target cells, focusing on the regulation of NK cell activating receptor (NKG2D, DNAM1) and inhibitory receptor (KIR2DL1-4, NKG2A, and LIR-1) signaling pathways. Inhibition of NK cell activity may protect xenografts from cytotoxicity. Recent successful approaches to reducing NK cell-mediated HXR and AXR are reviewed, including genetic modifications of porcine xenografts aimed at improving pig-to-human compatibility. Future directions to promote xenograft acceptance are discussed, including NK cell tolerance in pregnancy and NK cell evasion in viral infection.https://www.frontiersin.org/articles/10.3389/fimmu.2022.941880/fullNK cellsNK cell tolerancexenotransplantxenotranplantationtolerance |
| spellingShingle | Kevin J. Lopez Arthur A. Cross-Najafi Kristine Farag Benjamin Obando Deepthi Thadasina Abdulkadir Isidan Yujin Park Wenjun Zhang Burcin Ekser Ping Li Strategies to induce natural killer cell tolerance in xenotransplantation Frontiers in Immunology NK cells NK cell tolerance xenotransplant xenotranplantation tolerance |
| title | Strategies to induce natural killer cell tolerance in xenotransplantation |
| title_full | Strategies to induce natural killer cell tolerance in xenotransplantation |
| title_fullStr | Strategies to induce natural killer cell tolerance in xenotransplantation |
| title_full_unstemmed | Strategies to induce natural killer cell tolerance in xenotransplantation |
| title_short | Strategies to induce natural killer cell tolerance in xenotransplantation |
| title_sort | strategies to induce natural killer cell tolerance in xenotransplantation |
| topic | NK cells NK cell tolerance xenotransplant xenotranplantation tolerance |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.941880/full |
| work_keys_str_mv | AT kevinjlopez strategiestoinducenaturalkillercelltoleranceinxenotransplantation AT arthuracrossnajafi strategiestoinducenaturalkillercelltoleranceinxenotransplantation AT kristinefarag strategiestoinducenaturalkillercelltoleranceinxenotransplantation AT benjaminobando strategiestoinducenaturalkillercelltoleranceinxenotransplantation AT deepthithadasina strategiestoinducenaturalkillercelltoleranceinxenotransplantation AT abdulkadirisidan strategiestoinducenaturalkillercelltoleranceinxenotransplantation AT yujinpark strategiestoinducenaturalkillercelltoleranceinxenotransplantation AT wenjunzhang strategiestoinducenaturalkillercelltoleranceinxenotransplantation AT burcinekser strategiestoinducenaturalkillercelltoleranceinxenotransplantation AT pingli strategiestoinducenaturalkillercelltoleranceinxenotransplantation |