Interleukin-6 induces Gr-1+CD11b+ myeloid cells to suppress CD8+ T cell-mediated liver injury in mice
Agonist antibodies against CD137 (4-1BB) on T lymphocytes are used to increase host anti-tumor immunity, but often leading to severe liver injury in treated mice or in patients during clinical trials. Interleukin-6 (IL-6) has been reported to protect hepatocyte death, but the role of IL-6 in protect...
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| Veröffentlicht in: | PloS one 2011-03, Vol.6 (3), p.e17631-e17631 |
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| creator | Cheng, Liang Wang, Jun Li, Xiaozhu Xing, Qiao Du, Peishuang Su, Lishan Wang, Shengdian |
| description | Agonist antibodies against CD137 (4-1BB) on T lymphocytes are used to increase host anti-tumor immunity, but often leading to severe liver injury in treated mice or in patients during clinical trials. Interleukin-6 (IL-6) has been reported to protect hepatocyte death, but the role of IL-6 in protecting chronic T cell-induced liver diseases is not clearly defined due to lack of relevant animal models. We aimed to define the role of IL-6 in CD8+ T cell-mediated liver injury induced by a CD137 agonistic mAb (clone 2A) in mice.
We expressed IL-6 in the liver by hydrodynamic gene delivery in mice treated with 2A or control mAb and studied how IL-6 treatment affected host immunity and T cell-mediated liver injury. We found that ectopic IL-6 expression in the liver elevated intrahepatic leukocyte infiltration but prevented CD8+ T cell-mediated liver injury. In IL-6 treated mice, CD8+ T cells proliferation and IFN-γ expression were inhibited in the liver. We discovered that IL-6 increased accumulation of Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) in the liver and spleen. These MDSCs had the ability to inhibit T cells proliferation and activation. Finally, we showed that the MDSCs were sufficient and essential for IL-6-mediated protection of anti-CD137 mAb-induced liver injury.
We concluded that IL-6 induced Gr-1+CD11b+ MDSCs in the liver to inhibit T cell-mediated liver injury. The findings have defined a novel mechanism of IL-6 in protecting liver from CD8+ T cell-mediated injury. |
| doi_str_mv | 10.1371/journal.pone.0017631 |
| format | Article |
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We expressed IL-6 in the liver by hydrodynamic gene delivery in mice treated with 2A or control mAb and studied how IL-6 treatment affected host immunity and T cell-mediated liver injury. We found that ectopic IL-6 expression in the liver elevated intrahepatic leukocyte infiltration but prevented CD8+ T cell-mediated liver injury. In IL-6 treated mice, CD8+ T cells proliferation and IFN-γ expression were inhibited in the liver. We discovered that IL-6 increased accumulation of Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) in the liver and spleen. These MDSCs had the ability to inhibit T cells proliferation and activation. Finally, we showed that the MDSCs were sufficient and essential for IL-6-mediated protection of anti-CD137 mAb-induced liver injury.
We concluded that IL-6 induced Gr-1+CD11b+ MDSCs in the liver to inhibit T cell-mediated liver injury. The findings have defined a novel mechanism of IL-6 in protecting liver from CD8+ T cell-mediated injury.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0017631</identifier><identifier>PMID: 21394214</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alcohol ; Analysis ; Animal models ; Animals ; Antibodies ; Antigens ; Biology ; Biophysics ; CD11b antigen ; CD11b Antigen - metabolism ; CD137 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; Cell activation ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Cell-mediated immunity ; Clinical trials ; Cloning ; Cytokines ; Female ; Gender differences ; Gene transfer ; Hepatitis ; Hepatocytes ; Immunity ; Immunology ; Infections ; Infiltration ; Inflammation ; Injury prevention ; Interferon ; Interleukin 6 ; Interleukin-6 - administration & dosage ; Interleukin-6 - pharmacology ; Interleukins ; Laboratories ; Leukocytes ; Ligands ; Liver ; Liver - drug effects ; Liver - immunology ; Liver - pathology ; Liver cancer ; Liver diseases ; Liver Diseases - immunology ; Liver Diseases - pathology ; Liver Diseases - prevention & control ; Lymphocyte Activation - drug effects ; Lymphocyte Activation - immunology ; Lymphocytes ; Lymphocytes T ; Medical research ; Medicine ; Metastases ; Mice ; Mice, Inbred C57BL ; Monoclonal antibodies ; Myeloid cells ; Myeloid Cells - drug effects ; Myeloid Cells - metabolism ; Protective Agents - pharmacology ; Proteins ; Receptors, Chemokine - metabolism ; Rodents ; Spleen ; Spleen - drug effects ; Spleen - immunology ; Spleen - pathology ; Splenomegaly ; Suppressor cells ; T cells ; Transgenic animals ; Tumorigenesis ; Tumors ; Viruses ; γ-Interferon</subject><ispartof>PloS one, 2011-03, Vol.6 (3), p.e17631-e17631</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Cheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Cheng et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-5ffd864a1d45478d9c202cf6e000b21be6c77344ce26a11abefc616aa10b16c33</citedby><cites>FETCH-LOGICAL-c723t-5ffd864a1d45478d9c202cf6e000b21be6c77344ce26a11abefc616aa10b16c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048877/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048877/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21394214$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Eltzschig, Holger</contributor><creatorcontrib>Cheng, Liang</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Li, Xiaozhu</creatorcontrib><creatorcontrib>Xing, Qiao</creatorcontrib><creatorcontrib>Du, Peishuang</creatorcontrib><creatorcontrib>Su, Lishan</creatorcontrib><creatorcontrib>Wang, Shengdian</creatorcontrib><title>Interleukin-6 induces Gr-1+CD11b+ myeloid cells to suppress CD8+ T cell-mediated liver injury in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Agonist antibodies against CD137 (4-1BB) on T lymphocytes are used to increase host anti-tumor immunity, but often leading to severe liver injury in treated mice or in patients during clinical trials. Interleukin-6 (IL-6) has been reported to protect hepatocyte death, but the role of IL-6 in protecting chronic T cell-induced liver diseases is not clearly defined due to lack of relevant animal models. We aimed to define the role of IL-6 in CD8+ T cell-mediated liver injury induced by a CD137 agonistic mAb (clone 2A) in mice.
We expressed IL-6 in the liver by hydrodynamic gene delivery in mice treated with 2A or control mAb and studied how IL-6 treatment affected host immunity and T cell-mediated liver injury. We found that ectopic IL-6 expression in the liver elevated intrahepatic leukocyte infiltration but prevented CD8+ T cell-mediated liver injury. In IL-6 treated mice, CD8+ T cells proliferation and IFN-γ expression were inhibited in the liver. We discovered that IL-6 increased accumulation of Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) in the liver and spleen. These MDSCs had the ability to inhibit T cells proliferation and activation. Finally, we showed that the MDSCs were sufficient and essential for IL-6-mediated protection of anti-CD137 mAb-induced liver injury.
We concluded that IL-6 induced Gr-1+CD11b+ MDSCs in the liver to inhibit T cell-mediated liver injury. The findings have defined a novel mechanism of IL-6 in protecting liver from CD8+ T cell-mediated injury.</description><subject>Alcohol</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Biology</subject><subject>Biophysics</subject><subject>CD11b antigen</subject><subject>CD11b Antigen - metabolism</subject><subject>CD137 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell activation</subject><subject>Cell Movement - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell-mediated immunity</subject><subject>Clinical trials</subject><subject>Cloning</subject><subject>Cytokines</subject><subject>Female</subject><subject>Gender differences</subject><subject>Gene transfer</subject><subject>Hepatitis</subject><subject>Hepatocytes</subject><subject>Immunity</subject><subject>Immunology</subject><subject>Infections</subject><subject>Infiltration</subject><subject>Inflammation</subject><subject>Injury prevention</subject><subject>Interferon</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - administration & dosage</subject><subject>Interleukin-6 - pharmacology</subject><subject>Interleukins</subject><subject>Laboratories</subject><subject>Leukocytes</subject><subject>Ligands</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - immunology</subject><subject>Liver - pathology</subject><subject>Liver cancer</subject><subject>Liver diseases</subject><subject>Liver Diseases - immunology</subject><subject>Liver Diseases - pathology</subject><subject>Liver Diseases - prevention & control</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocyte Activation - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Metastases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Monoclonal antibodies</subject><subject>Myeloid cells</subject><subject>Myeloid Cells - drug effects</subject><subject>Myeloid Cells - metabolism</subject><subject>Protective Agents - pharmacology</subject><subject>Proteins</subject><subject>Receptors, Chemokine - metabolism</subject><subject>Rodents</subject><subject>Spleen</subject><subject>Spleen - drug effects</subject><subject>Spleen - immunology</subject><subject>Spleen - pathology</subject><subject>Splenomegaly</subject><subject>Suppressor cells</subject><subject>T cells</subject><subject>Transgenic animals</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Viruses</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1GL1DAQx4so3rn6DUQLgiJL10ySpu2LcOzpuXBwoKevIU2nu1m7zZq0h_vtzd72jq0cKHlImPnNP5mZTBS9BDIDlsGHte1dq5rZ1rY4IwQyweBRdAoFo4mghD0-Op9Ez7xfE5KyXIin0QkFVnAK_DTCRduha7D_adpExKateo0-vnAJTOfnAOU03uywsaaKNTaNjzsb-367deh9PD_Pp_H1rSPZYGVUh1XcmBt0QWjdu13Y4o3R-Dx6UqvG44thn0TfP3-6nn9JLq8uFvOzy0RnlHVJWtdVLriCiqc8y6tCU0J1LZAQUlIoUegsY5xrpEIBqBJrLUAoBaQEoRmbRK8PutvGejlUyEtgQCHLGU8DsTgQlVVruXVmo9xOWmXkrcG6pVSuM7pBmRalILoSrMyBZxQUrVIhtM6J4FAURdD6ONzWlyF9jW3nVDMSHXtas5JLeyMZ4XkeMplE7wYBZ3_16Du5MX5fTdWi7b0sSAYpTwn5J5mnIsuKNM0D-eYv8uEyDNRShUxNW9vwQL3XlGc8EwVhnIpAzR6gwqowdDX8u9oE-yjg_SggMB3-7paq914uvn39f_bqx5h9e8SuUDXdytum74xt_RjkB1A7673D-r4bQOR-bO6qIfdjI4exCWGvjjt5H3Q3J-wPlyoO-Q</recordid><startdate>20110304</startdate><enddate>20110304</enddate><creator>Cheng, Liang</creator><creator>Wang, Jun</creator><creator>Li, Xiaozhu</creator><creator>Xing, Qiao</creator><creator>Du, Peishuang</creator><creator>Su, Lishan</creator><creator>Wang, Shengdian</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110304</creationdate><title>Interleukin-6 induces Gr-1+CD11b+ myeloid cells to suppress CD8+ T cell-mediated liver injury in mice</title><author>Cheng, Liang ; Wang, Jun ; Li, Xiaozhu ; Xing, Qiao ; Du, Peishuang ; Su, Lishan ; Wang, Shengdian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c723t-5ffd864a1d45478d9c202cf6e000b21be6c77344ce26a11abefc616aa10b16c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Alcohol</topic><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Biology</topic><topic>Biophysics</topic><topic>CD11b antigen</topic><topic>CD11b Antigen - metabolism</topic><topic>CD137 antigen</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - drug effects</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell activation</topic><topic>Cell Movement - drug effects</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell-mediated immunity</topic><topic>Clinical trials</topic><topic>Cloning</topic><topic>Cytokines</topic><topic>Female</topic><topic>Gender differences</topic><topic>Gene transfer</topic><topic>Hepatitis</topic><topic>Hepatocytes</topic><topic>Immunity</topic><topic>Immunology</topic><topic>Infections</topic><topic>Infiltration</topic><topic>Inflammation</topic><topic>Injury prevention</topic><topic>Interferon</topic><topic>Interleukin 6</topic><topic>Interleukin-6 - administration & dosage</topic><topic>Interleukin-6 - pharmacology</topic><topic>Interleukins</topic><topic>Laboratories</topic><topic>Leukocytes</topic><topic>Ligands</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - immunology</topic><topic>Liver - pathology</topic><topic>Liver cancer</topic><topic>Liver diseases</topic><topic>Liver Diseases - immunology</topic><topic>Liver Diseases - pathology</topic><topic>Liver Diseases - prevention & control</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Lymphocyte Activation - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Metastases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Monoclonal antibodies</topic><topic>Myeloid cells</topic><topic>Myeloid Cells - drug effects</topic><topic>Myeloid Cells - metabolism</topic><topic>Protective Agents - pharmacology</topic><topic>Proteins</topic><topic>Receptors, Chemokine - metabolism</topic><topic>Rodents</topic><topic>Spleen</topic><topic>Spleen - drug effects</topic><topic>Spleen - immunology</topic><topic>Spleen - pathology</topic><topic>Splenomegaly</topic><topic>Suppressor cells</topic><topic>T cells</topic><topic>Transgenic animals</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Viruses</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Liang</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Li, Xiaozhu</creatorcontrib><creatorcontrib>Xing, Qiao</creatorcontrib><creatorcontrib>Du, Peishuang</creatorcontrib><creatorcontrib>Su, Lishan</creatorcontrib><creatorcontrib>Wang, Shengdian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Liang</au><au>Wang, Jun</au><au>Li, Xiaozhu</au><au>Xing, Qiao</au><au>Du, Peishuang</au><au>Su, Lishan</au><au>Wang, Shengdian</au><au>Eltzschig, Holger</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-6 induces Gr-1+CD11b+ myeloid cells to suppress CD8+ T cell-mediated liver injury in mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-03-04</date><risdate>2011</risdate><volume>6</volume><issue>3</issue><spage>e17631</spage><epage>e17631</epage><pages>e17631-e17631</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Agonist antibodies against CD137 (4-1BB) on T lymphocytes are used to increase host anti-tumor immunity, but often leading to severe liver injury in treated mice or in patients during clinical trials. Interleukin-6 (IL-6) has been reported to protect hepatocyte death, but the role of IL-6 in protecting chronic T cell-induced liver diseases is not clearly defined due to lack of relevant animal models. We aimed to define the role of IL-6 in CD8+ T cell-mediated liver injury induced by a CD137 agonistic mAb (clone 2A) in mice.
We expressed IL-6 in the liver by hydrodynamic gene delivery in mice treated with 2A or control mAb and studied how IL-6 treatment affected host immunity and T cell-mediated liver injury. We found that ectopic IL-6 expression in the liver elevated intrahepatic leukocyte infiltration but prevented CD8+ T cell-mediated liver injury. In IL-6 treated mice, CD8+ T cells proliferation and IFN-γ expression were inhibited in the liver. We discovered that IL-6 increased accumulation of Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) in the liver and spleen. These MDSCs had the ability to inhibit T cells proliferation and activation. Finally, we showed that the MDSCs were sufficient and essential for IL-6-mediated protection of anti-CD137 mAb-induced liver injury.
We concluded that IL-6 induced Gr-1+CD11b+ MDSCs in the liver to inhibit T cell-mediated liver injury. The findings have defined a novel mechanism of IL-6 in protecting liver from CD8+ T cell-mediated injury.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21394214</pmid><doi>10.1371/journal.pone.0017631</doi><tpages>e17631</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-03, Vol.6 (3), p.e17631-e17631 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312178345 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Alcohol Analysis Animal models Animals Antibodies Antigens Biology Biophysics CD11b antigen CD11b Antigen - metabolism CD137 antigen CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology Cell activation Cell Movement - drug effects Cell proliferation Cell Proliferation - drug effects Cell-mediated immunity Clinical trials Cloning Cytokines Female Gender differences Gene transfer Hepatitis Hepatocytes Immunity Immunology Infections Infiltration Inflammation Injury prevention Interferon Interleukin 6 Interleukin-6 - administration & dosage Interleukin-6 - pharmacology Interleukins Laboratories Leukocytes Ligands Liver Liver - drug effects Liver - immunology Liver - pathology Liver cancer Liver diseases Liver Diseases - immunology Liver Diseases - pathology Liver Diseases - prevention & control Lymphocyte Activation - drug effects Lymphocyte Activation - immunology Lymphocytes Lymphocytes T Medical research Medicine Metastases Mice Mice, Inbred C57BL Monoclonal antibodies Myeloid cells Myeloid Cells - drug effects Myeloid Cells - metabolism Protective Agents - pharmacology Proteins Receptors, Chemokine - metabolism Rodents Spleen Spleen - drug effects Spleen - immunology Spleen - pathology Splenomegaly Suppressor cells T cells Transgenic animals Tumorigenesis Tumors Viruses γ-Interferon |
| title | Interleukin-6 induces Gr-1+CD11b+ myeloid cells to suppress CD8+ T cell-mediated liver injury in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T07%3A08%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Interleukin-6%20induces%20Gr-1+CD11b+%20myeloid%20cells%20to%20suppress%20CD8+%20T%20cell-mediated%20liver%20injury%20in%20mice&rft.jtitle=PloS%20one&rft.au=Cheng,%20Liang&rft.date=2011-03-04&rft.volume=6&rft.issue=3&rft.spage=e17631&rft.epage=e17631&rft.pages=e17631-e17631&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0017631&rft_dat=%3Cgale_plos_%3EA476903426%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1312178345&rft_id=info:pmid/21394214&rft_galeid=A476903426&rft_doaj_id=oai_doaj_org_article_59b60cd63b814721a2d566cc80641999&rfr_iscdi=true |