Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f
NK cells participate in ischemia reperfusion injury (IRI) and transplant rejection. Endogenous regulatory systems may exist to attenuate NK cell activation and cytotoxicity in IRI associated with kidney transplantation. A greater understanding of NK regulation will provide insights in transplant out...
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Elsevier
2024-01-01
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| Series: | Current Research in Immunology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590255524000052 |
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| author | Benjamin Fuhrmann Jifu Jiang Patrick Mcleod Xuyan Huang Shilpa Balaji Jaqueline Arp Hong Diao Shengwu Ma Tianqing Peng Aaron Haig Lakshman Gunaratnam Zhu-Xu Zhang Anthony M. Jevnikar |
| author_facet | Benjamin Fuhrmann Jifu Jiang Patrick Mcleod Xuyan Huang Shilpa Balaji Jaqueline Arp Hong Diao Shengwu Ma Tianqing Peng Aaron Haig Lakshman Gunaratnam Zhu-Xu Zhang Anthony M. Jevnikar |
| author_sort | Benjamin Fuhrmann |
| collection | DOAJ |
| description | NK cells participate in ischemia reperfusion injury (IRI) and transplant rejection. Endogenous regulatory systems may exist to attenuate NK cell activation and cytotoxicity in IRI associated with kidney transplantation. A greater understanding of NK regulation will provide insights in transplant outcomes and could direct new therapeutic strategies. Kidney tubular epithelial cells (TECs) may negatively regulate NK cell activation by their surface expression of a complex family of C-type lectin-related proteins (Clrs). We have found that Clr-b and Clr-f were expressed by TECs. Clr-b was upregulated by inflammatory cytokines TNFα and IFNγ in vitro. Silencing of both Clr-b and Clr-f expression using siRNA resulted in increased NK cell killing of TECs compared to silencing of either Clr-b or Clr-f alone (p < 0.01) and when compared to control TECs (p < 0.001). NK cells treated in vitro with soluble Clr-b and Clr-f proteins reduced their capacity to kill TECs (p < 0.05). Hence, NK cell cytotoxicity can be inhibited by Clr proteins on the surface of TECs. Our study suggests a synergistic effect of Clr molecules in regulating NK cell function in renal cells and this may represent an important endogenous regulatory system to limit NK cell-mediated organ injury during inflammation. |
| format | Article |
| id | doaj-art-041f61a5438b4d56970ed3d49f5b1c8e |
| institution | Kabale University |
| issn | 2590-2555 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Immunology |
| spelling | doaj-art-041f61a5438b4d56970ed3d49f5b1c8e2024-12-06T05:14:29ZengElsevierCurrent Research in Immunology2590-25552024-01-015100081Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-fBenjamin Fuhrmann0Jifu Jiang1Patrick Mcleod2Xuyan Huang3Shilpa Balaji4Jaqueline Arp5Hong Diao6Shengwu Ma7Tianqing Peng8Aaron Haig9Lakshman Gunaratnam10Zhu-Xu Zhang11Anthony M. Jevnikar12Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Microbiology and Immunology, Western University, London, Ontario, CanadaMatthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, CanadaMatthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, CanadaMatthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, CanadaMatthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Microbiology and Immunology, Western University, London, Ontario, CanadaMatthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, CanadaMatthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, CanadaDepartment of Microbiology and Immunology, Western University, London, Ontario, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, Ontario, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, Ontario, CanadaMatthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Multi-Organ Transplantation Program, London Health Sciences Centre, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, CanadaMatthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; Multi-Organ Transplantation Program, London Health Sciences Centre, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Corresponding author. Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada.Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Multi-Organ Transplantation Program, London Health Sciences Centre, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Corresponding author. Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada.NK cells participate in ischemia reperfusion injury (IRI) and transplant rejection. Endogenous regulatory systems may exist to attenuate NK cell activation and cytotoxicity in IRI associated with kidney transplantation. A greater understanding of NK regulation will provide insights in transplant outcomes and could direct new therapeutic strategies. Kidney tubular epithelial cells (TECs) may negatively regulate NK cell activation by their surface expression of a complex family of C-type lectin-related proteins (Clrs). We have found that Clr-b and Clr-f were expressed by TECs. Clr-b was upregulated by inflammatory cytokines TNFα and IFNγ in vitro. Silencing of both Clr-b and Clr-f expression using siRNA resulted in increased NK cell killing of TECs compared to silencing of either Clr-b or Clr-f alone (p < 0.01) and when compared to control TECs (p < 0.001). NK cells treated in vitro with soluble Clr-b and Clr-f proteins reduced their capacity to kill TECs (p < 0.05). Hence, NK cell cytotoxicity can be inhibited by Clr proteins on the surface of TECs. Our study suggests a synergistic effect of Clr molecules in regulating NK cell function in renal cells and this may represent an important endogenous regulatory system to limit NK cell-mediated organ injury during inflammation.http://www.sciencedirect.com/science/article/pii/S2590255524000052NK cellClr-bClr-fTECKidney |
| spellingShingle | Benjamin Fuhrmann Jifu Jiang Patrick Mcleod Xuyan Huang Shilpa Balaji Jaqueline Arp Hong Diao Shengwu Ma Tianqing Peng Aaron Haig Lakshman Gunaratnam Zhu-Xu Zhang Anthony M. Jevnikar Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f Current Research in Immunology NK cell Clr-b Clr-f TEC Kidney |
| title | Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f |
| title_full | Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f |
| title_fullStr | Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f |
| title_full_unstemmed | Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f |
| title_short | Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f |
| title_sort | inhibition of nk cell cytotoxicity by tubular epithelial cell expression of clr b and clr f |
| topic | NK cell Clr-b Clr-f TEC Kidney |
| url | http://www.sciencedirect.com/science/article/pii/S2590255524000052 |
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