Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis
Neutrophils are potent effector cells and contain a battery of harmful substances and degrading enzymes. A silent neutrophil death, i.e., apoptosis, is therefore of importance to avoid damage to the surrounding tissue and to enable termination of the acute inflammatory process. There is a pile of ev...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02444/full |
| _version_ | 1828532145105141760 |
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| author | Elin Bernson Elin Bernson Karin Christenson Karin Christenson Karin Christenson Silvia Pesce Silvia Pesce Silvia Pesce Malin Pasanen Malin Pasanen Emanuela Marcenaro Emanuela Marcenaro Simona Sivori Simona Sivori Fredrik B. Thorén Fredrik B. Thorén |
| author_facet | Elin Bernson Elin Bernson Karin Christenson Karin Christenson Karin Christenson Silvia Pesce Silvia Pesce Silvia Pesce Malin Pasanen Malin Pasanen Emanuela Marcenaro Emanuela Marcenaro Simona Sivori Simona Sivori Fredrik B. Thorén Fredrik B. Thorén |
| author_sort | Elin Bernson |
| collection | DOAJ |
| description | Neutrophils are potent effector cells and contain a battery of harmful substances and degrading enzymes. A silent neutrophil death, i.e., apoptosis, is therefore of importance to avoid damage to the surrounding tissue and to enable termination of the acute inflammatory process. There is a pile of evidence supporting the role for pro-inflammatory cytokines in extending the life-span of neutrophils, but relatively few studies have been devoted to mechanisms actively driving apoptosis induction in neutrophils. We have previously demonstrated that natural killer (NK) cells can promote apoptosis in healthy neutrophils. In this study, we set out to investigate how neutrophil sensitivity to NK cell-mediated cytotoxicity is regulated under inflammatory conditions. Using in vitro-activated neutrophils and a human skin chamber model that allowed collection of in vivo-transmigrated neutrophils, we performed a comprehensive characterization of neutrophil expression of ligands to NK cell receptors. These studies revealed a dramatic downregulation of HLA class I molecules in inflammatory neutrophils, which was associated with an enhanced susceptibility to NK cell cytotoxicity. Collectively, our data shed light on the complex regulation of interactions between NK cells and neutrophils during an inflammatory response and provide further support for a role of NK cells in the resolution phase of inflammation. |
| first_indexed | 2024-12-11T22:48:08Z |
| format | Article |
| id | doaj.art-13aa5988cc61480783dec0b3af192754 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T22:48:08Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-13aa5988cc61480783dec0b3af1927542022-12-22T00:47:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02444473981Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced ApoptosisElin Bernson0Elin Bernson1Karin Christenson2Karin Christenson3Karin Christenson4Silvia Pesce5Silvia Pesce6Silvia Pesce7Malin Pasanen8Malin Pasanen9Emanuela Marcenaro10Emanuela Marcenaro11Simona Sivori12Simona Sivori13Fredrik B. Thorén14Fredrik B. Thorén15TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, SwedenDepartment of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenTIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, SwedenDepartment of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Oral Microbiology and Immunology, University of Gothenburg, Gothenburg, SwedenTIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, SwedenDepartment of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Experimental Medicine, University of Genoa, Genoa, ItalyTIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, SwedenDepartment of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Experimental Medicine, University of Genoa, Genoa, ItalyCenter of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, ItalyDepartment of Experimental Medicine, University of Genoa, Genoa, ItalyCenter of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, ItalyTIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, SwedenDepartment of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenNeutrophils are potent effector cells and contain a battery of harmful substances and degrading enzymes. A silent neutrophil death, i.e., apoptosis, is therefore of importance to avoid damage to the surrounding tissue and to enable termination of the acute inflammatory process. There is a pile of evidence supporting the role for pro-inflammatory cytokines in extending the life-span of neutrophils, but relatively few studies have been devoted to mechanisms actively driving apoptosis induction in neutrophils. We have previously demonstrated that natural killer (NK) cells can promote apoptosis in healthy neutrophils. In this study, we set out to investigate how neutrophil sensitivity to NK cell-mediated cytotoxicity is regulated under inflammatory conditions. Using in vitro-activated neutrophils and a human skin chamber model that allowed collection of in vivo-transmigrated neutrophils, we performed a comprehensive characterization of neutrophil expression of ligands to NK cell receptors. These studies revealed a dramatic downregulation of HLA class I molecules in inflammatory neutrophils, which was associated with an enhanced susceptibility to NK cell cytotoxicity. Collectively, our data shed light on the complex regulation of interactions between NK cells and neutrophils during an inflammatory response and provide further support for a role of NK cells in the resolution phase of inflammation.https://www.frontiersin.org/article/10.3389/fimmu.2019.02444/fullneutrophilNK cellHLA class Iimmunoregulationneutrophil apoptosis |
| spellingShingle | Elin Bernson Elin Bernson Karin Christenson Karin Christenson Karin Christenson Silvia Pesce Silvia Pesce Silvia Pesce Malin Pasanen Malin Pasanen Emanuela Marcenaro Emanuela Marcenaro Simona Sivori Simona Sivori Fredrik B. Thorén Fredrik B. Thorén Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis Frontiers in Immunology neutrophil NK cell HLA class I immunoregulation neutrophil apoptosis |
| title | Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis |
| title_full | Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis |
| title_fullStr | Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis |
| title_full_unstemmed | Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis |
| title_short | Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis |
| title_sort | downregulation of hla class i renders inflammatory neutrophils more susceptible to nk cell induced apoptosis |
| topic | neutrophil NK cell HLA class I immunoregulation neutrophil apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02444/full |
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