Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model
Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell–mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here...
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description | Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell–mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti‐NK1.1 antibody attenuated bronchiolitis obliterans in transplant recipients compared with controls. In terms of NK cell effector functions, an improvement in bronchiolitis obliterans was observed in perforin‐KO recipient mice compared to wild type (WT). Furthermore, we found upregulation of NKG2D‐ligand in allografts and demonstrated the significance of this using grafts expressing Rae‐1, a murine NKG2D‐ligand, which induced severe bronchiolitis obliterans in WT and Rag‐1 KO recipients. This effect was ameliorated by injection of anti‐NKG2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans.
In a murine heterotopic tracheal transplant model, cytotoxicity of natural killer cells activated through NKG2D plays an important role in the development of bronchiolitis obliterans. |
doi_str_mv | 10.1111/ajt.14257 |
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In a murine heterotopic tracheal transplant model, cytotoxicity of natural killer cells activated through NKG2D plays an important role in the development of bronchiolitis obliterans.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.14257</identifier><identifier>PMID: 28251796</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Allografts ; Animals ; basic (laboratory) research/science ; Bronchiolitis obliterans ; bronchiolitis obliterans (BOS) ; Bronchiolitis Obliterans - etiology ; Bronchiolitis Obliterans - metabolism ; Bronchiolitis Obliterans - pathology ; Bronchopneumonia ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cell-mediated immunity ; Cells, Cultured ; Cytotoxicity ; Disease Models, Animal ; Graft Rejection - etiology ; Graft Rejection - metabolism ; Graft Rejection - pathology ; Homeodomain Proteins - physiology ; Immunity, Cellular ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Killer Cells, Natural - pathology ; Ligands ; Lung transplantation ; lung transplantation/pulmonology ; Lymphocytes T ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID ; natural killer (NK) cells/NK receptors ; Natural killer cells ; NK Cell Lectin-Like Receptor Subfamily K - metabolism ; NKG2 antigen ; Perforin ; Syngeneic grafts ; Trachea - transplantation ; Transplantation ; Transplantation, Heterotopic - adverse effects ; Transplants & implants ; Xenografts</subject><ispartof>American journal of transplantation, 2017-09, Vol.17 (9), p.2338-2349</ispartof><rights>2017 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>2017 The American Society of Transplantation and the American Society of Transplant Surgeons.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4547-14cc1d7e38cb05073679d53670d5d54622d3aa33c1bb0e425a881f2cf19f183c3</citedby><cites>FETCH-LOGICAL-c4547-14cc1d7e38cb05073679d53670d5d54622d3aa33c1bb0e425a881f2cf19f183c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fajt.14257$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.14257$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28251796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawakami, T.</creatorcontrib><creatorcontrib>Ito, K.</creatorcontrib><creatorcontrib>Matsuda, Y.</creatorcontrib><creatorcontrib>Noda, M.</creatorcontrib><creatorcontrib>Sakurada, A.</creatorcontrib><creatorcontrib>Hoshikawa, Y.</creatorcontrib><creatorcontrib>Okada, Y.</creatorcontrib><creatorcontrib>Ogasawara, K.</creatorcontrib><title>Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell–mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti‐NK1.1 antibody attenuated bronchiolitis obliterans in transplant recipients compared with controls. In terms of NK cell effector functions, an improvement in bronchiolitis obliterans was observed in perforin‐KO recipient mice compared to wild type (WT). Furthermore, we found upregulation of NKG2D‐ligand in allografts and demonstrated the significance of this using grafts expressing Rae‐1, a murine NKG2D‐ligand, which induced severe bronchiolitis obliterans in WT and Rag‐1 KO recipients. This effect was ameliorated by injection of anti‐NKG2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans.
In a murine heterotopic tracheal transplant model, cytotoxicity of natural killer cells activated through NKG2D plays an important role in the development of bronchiolitis obliterans.</description><subject>Allografts</subject><subject>Animals</subject><subject>basic (laboratory) research/science</subject><subject>Bronchiolitis obliterans</subject><subject>bronchiolitis obliterans (BOS)</subject><subject>Bronchiolitis Obliterans - etiology</subject><subject>Bronchiolitis Obliterans - metabolism</subject><subject>Bronchiolitis Obliterans - pathology</subject><subject>Bronchopneumonia</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell-mediated immunity</subject><subject>Cells, Cultured</subject><subject>Cytotoxicity</subject><subject>Disease Models, Animal</subject><subject>Graft Rejection - etiology</subject><subject>Graft Rejection - metabolism</subject><subject>Graft Rejection - pathology</subject><subject>Homeodomain Proteins - physiology</subject><subject>Immunity, Cellular</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Killer Cells, Natural - pathology</subject><subject>Ligands</subject><subject>Lung transplantation</subject><subject>lung transplantation/pulmonology</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, SCID</subject><subject>natural killer (NK) cells/NK receptors</subject><subject>Natural killer cells</subject><subject>NK Cell Lectin-Like Receptor Subfamily K - metabolism</subject><subject>NKG2 antigen</subject><subject>Perforin</subject><subject>Syngeneic grafts</subject><subject>Trachea - transplantation</subject><subject>Transplantation</subject><subject>Transplantation, Heterotopic - adverse effects</subject><subject>Transplants & implants</subject><subject>Xenografts</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1P3DAQhi1EVSjtgT-ALHFpDwv-SOLkuIQWWr4u6dlynAnxyhsH26Hdn9R_WW-XcqhUH2ZG1qNHo3kROqbkjKZ3rlbxjGYsF3vokBaELAqa8f3XmecH6F0IK0KoYCV7iw5SzamoikP0q95EF91Po03cYNfjexVnryy-MdaCxzVYG_BSR_OsInS4GbybHwd8f3PFLnHtxuhNO0cIODocB8CX8AzWTWsY41Z34d2oB-OsiSbghzZ18GoM2IxY4bvZmxHwNaTPtMVkNG680gOkBZotNlmVPHeuA_sevemVDfDhpR-h718-N_X14vbh6mu9vF3oLM_EgmZa004AL3VLciJ4IaouT5V0eZdnBWMdV4pzTduWQDqaKkvaM93Tqqcl1_wIfdx5J--eZghRrk3Q6QxqBDcHSUvBBWNMVAk9_QddudmPaTtJK87KihWMJ-rTjtLeheChl5M3a-U3khK5zU-m_OSf_BJ78mKc2zV0r-TfwBJwvgN-GAub_5vk8luzU_4GfHql8A</recordid><startdate>201709</startdate><enddate>201709</enddate><creator>Kawakami, T.</creator><creator>Ito, K.</creator><creator>Matsuda, Y.</creator><creator>Noda, M.</creator><creator>Sakurada, A.</creator><creator>Hoshikawa, Y.</creator><creator>Okada, Y.</creator><creator>Ogasawara, K.</creator><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201709</creationdate><title>Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model</title><author>Kawakami, T. ; Ito, K. ; Matsuda, Y. ; Noda, M. ; Sakurada, A. ; Hoshikawa, Y. ; Okada, Y. ; Ogasawara, K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4547-14cc1d7e38cb05073679d53670d5d54622d3aa33c1bb0e425a881f2cf19f183c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Allografts</topic><topic>Animals</topic><topic>basic (laboratory) research/science</topic><topic>Bronchiolitis obliterans</topic><topic>bronchiolitis obliterans (BOS)</topic><topic>Bronchiolitis Obliterans - etiology</topic><topic>Bronchiolitis Obliterans - metabolism</topic><topic>Bronchiolitis Obliterans - pathology</topic><topic>Bronchopneumonia</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell-mediated immunity</topic><topic>Cells, Cultured</topic><topic>Cytotoxicity</topic><topic>Disease Models, Animal</topic><topic>Graft Rejection - etiology</topic><topic>Graft Rejection - metabolism</topic><topic>Graft Rejection - pathology</topic><topic>Homeodomain Proteins - physiology</topic><topic>Immunity, Cellular</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Killer Cells, Natural - pathology</topic><topic>Ligands</topic><topic>Lung transplantation</topic><topic>lung transplantation/pulmonology</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, SCID</topic><topic>natural killer (NK) cells/NK receptors</topic><topic>Natural killer cells</topic><topic>NK Cell Lectin-Like Receptor Subfamily K - metabolism</topic><topic>NKG2 antigen</topic><topic>Perforin</topic><topic>Syngeneic grafts</topic><topic>Trachea - transplantation</topic><topic>Transplantation</topic><topic>Transplantation, Heterotopic - adverse effects</topic><topic>Transplants & implants</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawakami, T.</creatorcontrib><creatorcontrib>Ito, K.</creatorcontrib><creatorcontrib>Matsuda, Y.</creatorcontrib><creatorcontrib>Noda, M.</creatorcontrib><creatorcontrib>Sakurada, A.</creatorcontrib><creatorcontrib>Hoshikawa, Y.</creatorcontrib><creatorcontrib>Okada, Y.</creatorcontrib><creatorcontrib>Ogasawara, K.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawakami, T.</au><au>Ito, K.</au><au>Matsuda, Y.</au><au>Noda, M.</au><au>Sakurada, A.</au><au>Hoshikawa, Y.</au><au>Okada, Y.</au><au>Ogasawara, K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2017-09</date><risdate>2017</risdate><volume>17</volume><issue>9</issue><spage>2338</spage><epage>2349</epage><pages>2338-2349</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell–mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti‐NK1.1 antibody attenuated bronchiolitis obliterans in transplant recipients compared with controls. In terms of NK cell effector functions, an improvement in bronchiolitis obliterans was observed in perforin‐KO recipient mice compared to wild type (WT). Furthermore, we found upregulation of NKG2D‐ligand in allografts and demonstrated the significance of this using grafts expressing Rae‐1, a murine NKG2D‐ligand, which induced severe bronchiolitis obliterans in WT and Rag‐1 KO recipients. This effect was ameliorated by injection of anti‐NKG2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans.
In a murine heterotopic tracheal transplant model, cytotoxicity of natural killer cells activated through NKG2D plays an important role in the development of bronchiolitis obliterans.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>28251796</pmid><doi>10.1111/ajt.14257</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Allografts Animals basic (laboratory) research/science Bronchiolitis obliterans bronchiolitis obliterans (BOS) Bronchiolitis Obliterans - etiology Bronchiolitis Obliterans - metabolism Bronchiolitis Obliterans - pathology Bronchopneumonia CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell-mediated immunity Cells, Cultured Cytotoxicity Disease Models, Animal Graft Rejection - etiology Graft Rejection - metabolism Graft Rejection - pathology Homeodomain Proteins - physiology Immunity, Cellular Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Killer Cells, Natural - pathology Ligands Lung transplantation lung transplantation/pulmonology Lymphocytes T Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, SCID natural killer (NK) cells/NK receptors Natural killer cells NK Cell Lectin-Like Receptor Subfamily K - metabolism NKG2 antigen Perforin Syngeneic grafts Trachea - transplantation Transplantation Transplantation, Heterotopic - adverse effects Transplants & implants Xenografts |
title | Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model |
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