Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model
Engraftment of IL-6 deficient donor into wild-type recipient could significantly improve allograft survival through T cell lineage particularly regulatory T cells (Tregs) in non-sensitized transplant host. However, its effect on innate immune responses remains uncertain. Our data revealed that donor...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-10, Vol.8 (10), p.e77559-e77559 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e77559 |
|---|---|
| container_issue | 10 |
| container_start_page | e77559 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Ge, Fangmin Yuan, Shunzong Su, Lida Shen, Zhonghua He, Aibin Huang, Tao Gong, Weihua |
| description | Engraftment of IL-6 deficient donor into wild-type recipient could significantly improve allograft survival through T cell lineage particularly regulatory T cells (Tregs) in non-sensitized transplant host. However, its effect on innate immune responses remains uncertain. Our data revealed that donor IL-6 deficiency significantly increased infiltration of two subsets of MDSCs (CD11b+Gr1+myeloid-derived suppressor cells), CD11b+Gr1(-low) and CD11b+Gr1(-int) with strong immunosuppression activity in the transplanted graft. It resulted in a dramatic increase of CD11b+Gr1(-low) frequency and a significant decrease of the frequency of CD11b+Gr1(-high) and CD4-CD8-NK1.1+ cells in the recipient's spleen. Unexpectedly, donor IL-6 deficiency could not significantly reduce macrophage frequency irrespective of in the host's spleen or graft. Taken together, suppression of innate immune effector cells and enhanced activity of regulatory MDSCs contributed to tolerance induction by blockade of IL-6 signaling pathway. The unveiled novel mechanism of targeting IL-6 might shed light on clinical therapeutic application in preventing accelerated allograft rejection for those pre-sensitized transplant recipients. |
| doi_str_mv | 10.1371/journal.pone.0077559 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1442701952</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478246536</galeid><doaj_id>oai_doaj_org_article_8f83f84911da4e4ab7cdfe35bbbada79</doaj_id><sourcerecordid>A478246536</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-7c804502734567681df74eeeb2e1a775accb6c3f530cc701a9b6c72e1049e78b3</originalsourceid><addsrcrecordid>eNqNk12P1CAUhhujcdfVf2CUxMToxYxQaGlvTCYbPyaZZBO_bpHC6QyTFmaBGsdfL7PT3UzNXhguoPCcl76Hc7LsOcFzQjl5t3WDt7Kb75yFOcacF0X9IDsnNc1nZY7pw5P1WfYkhC3GBa3K8nF2ljPCOM7ZefZz0UXwMhpnkWuRsVZGQKbvB2viHjV7pJ11Hi1XsxJpaI0yYNU-gUiinYcANpho_oBGG5A-ouilDbtO2oh6p6F7mj1qZRfg2ThfZN8_fvh2-Xm2uvq0vFysZooXVZxxVWFW4JxTVpS8rIhuOQOAJgcikzepVFMq2hYUK8UxkXX65OkQsxp41dCL7OVRd9e5IMbkBEEYyxNeF3kilkdCO7kVO2966ffCSSNuNpxfi2TAqA5E1Va0rVhNiJYMmGy40i3QomkaqSWvk9b78bah6UErsMl3NxGdnlizEWv3S1BeJzc0CbwZBby7HiBE0ZugoEuJAzfc_DejNa3zMqGv_kHvdzdSa5kMGNu6dK86iIoF41XOyoIetOb3UGlo6I1KldSatD8JeDsJSEyE33EthxDE8uuX_2evfkzZ1ydsKp0uboLrhkMhhinIjqDyLgQP7V2SCRaHRrjNhjg0ghgbIYW9OH2gu6Dbyqd_AcXwA6s</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1442701952</pqid></control><display><type>article</type><title>Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Ge, Fangmin ; Yuan, Shunzong ; Su, Lida ; Shen, Zhonghua ; He, Aibin ; Huang, Tao ; Gong, Weihua</creator><creatorcontrib>Ge, Fangmin ; Yuan, Shunzong ; Su, Lida ; Shen, Zhonghua ; He, Aibin ; Huang, Tao ; Gong, Weihua</creatorcontrib><description>Engraftment of IL-6 deficient donor into wild-type recipient could significantly improve allograft survival through T cell lineage particularly regulatory T cells (Tregs) in non-sensitized transplant host. However, its effect on innate immune responses remains uncertain. Our data revealed that donor IL-6 deficiency significantly increased infiltration of two subsets of MDSCs (CD11b+Gr1+myeloid-derived suppressor cells), CD11b+Gr1(-low) and CD11b+Gr1(-int) with strong immunosuppression activity in the transplanted graft. It resulted in a dramatic increase of CD11b+Gr1(-low) frequency and a significant decrease of the frequency of CD11b+Gr1(-high) and CD4-CD8-NK1.1+ cells in the recipient's spleen. Unexpectedly, donor IL-6 deficiency could not significantly reduce macrophage frequency irrespective of in the host's spleen or graft. Taken together, suppression of innate immune effector cells and enhanced activity of regulatory MDSCs contributed to tolerance induction by blockade of IL-6 signaling pathway. The unveiled novel mechanism of targeting IL-6 might shed light on clinical therapeutic application in preventing accelerated allograft rejection for those pre-sensitized transplant recipients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0077559</identifier><identifier>PMID: 24147024</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Allografts - immunology ; Allografts - metabolism ; Allografts - pathology ; Animals ; CD11b antigen ; CD11b Antigen - metabolism ; CD4 antigen ; CD8 antigen ; Cell lineage ; Cell survival ; Chemokines ; Coronary vessels ; Cytokines ; Data processing ; Effector cells ; Gene expression ; Graft rejection ; Graft Survival ; Health aspects ; Heart ; Heart Transplantation ; Immune response ; Immunity ; Immunity, Innate - genetics ; Immunological tolerance ; Immunophenotyping ; Immunoregulation ; Immunosuppression ; Immunotherapy ; Infiltration ; Innate immunity ; Interleukin 6 ; Interleukin-6 - deficiency ; Ischemia ; Lymphocytes ; Lymphocytes T ; Macrophages ; Male ; Medicine ; Mice ; Mice, Knockout ; Mitochondrial DNA ; Models, Animal ; Myeloid Cells - immunology ; Myeloid Cells - metabolism ; Myeloid Cells - pathology ; Organ transplant recipients ; Phenotype ; Pulmonary arteries ; Signal transduction ; Signaling ; Spleen ; Suppressor cells ; Surgery ; T cells ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; Transplantation Immunology - genetics ; Transplants & implants</subject><ispartof>PloS one, 2013-10, Vol.8 (10), p.e77559-e77559</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Ge 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>2013 Ge et al 2013 Ge et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-7c804502734567681df74eeeb2e1a775accb6c3f530cc701a9b6c72e1049e78b3</citedby><cites>FETCH-LOGICAL-c758t-7c804502734567681df74eeeb2e1a775accb6c3f530cc701a9b6c72e1049e78b3</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/PMC3797753/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797753/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24147024$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ge, Fangmin</creatorcontrib><creatorcontrib>Yuan, Shunzong</creatorcontrib><creatorcontrib>Su, Lida</creatorcontrib><creatorcontrib>Shen, Zhonghua</creatorcontrib><creatorcontrib>He, Aibin</creatorcontrib><creatorcontrib>Huang, Tao</creatorcontrib><creatorcontrib>Gong, Weihua</creatorcontrib><title>Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Engraftment of IL-6 deficient donor into wild-type recipient could significantly improve allograft survival through T cell lineage particularly regulatory T cells (Tregs) in non-sensitized transplant host. However, its effect on innate immune responses remains uncertain. Our data revealed that donor IL-6 deficiency significantly increased infiltration of two subsets of MDSCs (CD11b+Gr1+myeloid-derived suppressor cells), CD11b+Gr1(-low) and CD11b+Gr1(-int) with strong immunosuppression activity in the transplanted graft. It resulted in a dramatic increase of CD11b+Gr1(-low) frequency and a significant decrease of the frequency of CD11b+Gr1(-high) and CD4-CD8-NK1.1+ cells in the recipient's spleen. Unexpectedly, donor IL-6 deficiency could not significantly reduce macrophage frequency irrespective of in the host's spleen or graft. Taken together, suppression of innate immune effector cells and enhanced activity of regulatory MDSCs contributed to tolerance induction by blockade of IL-6 signaling pathway. The unveiled novel mechanism of targeting IL-6 might shed light on clinical therapeutic application in preventing accelerated allograft rejection for those pre-sensitized transplant recipients.</description><subject>Allografts - immunology</subject><subject>Allografts - metabolism</subject><subject>Allografts - pathology</subject><subject>Animals</subject><subject>CD11b antigen</subject><subject>CD11b Antigen - metabolism</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell lineage</subject><subject>Cell survival</subject><subject>Chemokines</subject><subject>Coronary vessels</subject><subject>Cytokines</subject><subject>Data processing</subject><subject>Effector cells</subject><subject>Gene expression</subject><subject>Graft rejection</subject><subject>Graft Survival</subject><subject>Health aspects</subject><subject>Heart</subject><subject>Heart Transplantation</subject><subject>Immune response</subject><subject>Immunity</subject><subject>Immunity, Innate - genetics</subject><subject>Immunological tolerance</subject><subject>Immunophenotyping</subject><subject>Immunoregulation</subject><subject>Immunosuppression</subject><subject>Immunotherapy</subject><subject>Infiltration</subject><subject>Innate immunity</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - deficiency</subject><subject>Ischemia</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mitochondrial DNA</subject><subject>Models, Animal</subject><subject>Myeloid Cells - immunology</subject><subject>Myeloid Cells - metabolism</subject><subject>Myeloid Cells - pathology</subject><subject>Organ transplant recipients</subject><subject>Phenotype</subject><subject>Pulmonary arteries</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Spleen</subject><subject>Suppressor cells</subject><subject>Surgery</subject><subject>T cells</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>Transplantation Immunology - genetics</subject><subject>Transplants & implants</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12P1CAUhhujcdfVf2CUxMToxYxQaGlvTCYbPyaZZBO_bpHC6QyTFmaBGsdfL7PT3UzNXhguoPCcl76Hc7LsOcFzQjl5t3WDt7Kb75yFOcacF0X9IDsnNc1nZY7pw5P1WfYkhC3GBa3K8nF2ljPCOM7ZefZz0UXwMhpnkWuRsVZGQKbvB2viHjV7pJ11Hi1XsxJpaI0yYNU-gUiinYcANpho_oBGG5A-ouilDbtO2oh6p6F7mj1qZRfg2ThfZN8_fvh2-Xm2uvq0vFysZooXVZxxVWFW4JxTVpS8rIhuOQOAJgcikzepVFMq2hYUK8UxkXX65OkQsxp41dCL7OVRd9e5IMbkBEEYyxNeF3kilkdCO7kVO2966ffCSSNuNpxfi2TAqA5E1Va0rVhNiJYMmGy40i3QomkaqSWvk9b78bah6UErsMl3NxGdnlizEWv3S1BeJzc0CbwZBby7HiBE0ZugoEuJAzfc_DejNa3zMqGv_kHvdzdSa5kMGNu6dK86iIoF41XOyoIetOb3UGlo6I1KldSatD8JeDsJSEyE33EthxDE8uuX_2evfkzZ1ydsKp0uboLrhkMhhinIjqDyLgQP7V2SCRaHRrjNhjg0ghgbIYW9OH2gu6Dbyqd_AcXwA6s</recordid><startdate>20131016</startdate><enddate>20131016</enddate><creator>Ge, Fangmin</creator><creator>Yuan, Shunzong</creator><creator>Su, Lida</creator><creator>Shen, Zhonghua</creator><creator>He, Aibin</creator><creator>Huang, Tao</creator><creator>Gong, Weihua</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>AEUYN</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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131016</creationdate><title>Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model</title><author>Ge, Fangmin ; Yuan, Shunzong ; Su, Lida ; Shen, Zhonghua ; He, Aibin ; Huang, Tao ; Gong, Weihua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-7c804502734567681df74eeeb2e1a775accb6c3f530cc701a9b6c72e1049e78b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Allografts - immunology</topic><topic>Allografts - metabolism</topic><topic>Allografts - pathology</topic><topic>Animals</topic><topic>CD11b antigen</topic><topic>CD11b Antigen - metabolism</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Cell lineage</topic><topic>Cell survival</topic><topic>Chemokines</topic><topic>Coronary vessels</topic><topic>Cytokines</topic><topic>Data processing</topic><topic>Effector cells</topic><topic>Gene expression</topic><topic>Graft rejection</topic><topic>Graft Survival</topic><topic>Health aspects</topic><topic>Heart</topic><topic>Heart Transplantation</topic><topic>Immune response</topic><topic>Immunity</topic><topic>Immunity, Innate - genetics</topic><topic>Immunological tolerance</topic><topic>Immunophenotyping</topic><topic>Immunoregulation</topic><topic>Immunosuppression</topic><topic>Immunotherapy</topic><topic>Infiltration</topic><topic>Innate immunity</topic><topic>Interleukin 6</topic><topic>Interleukin-6 - deficiency</topic><topic>Ischemia</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mitochondrial DNA</topic><topic>Models, Animal</topic><topic>Myeloid Cells - immunology</topic><topic>Myeloid Cells - metabolism</topic><topic>Myeloid Cells - pathology</topic><topic>Organ transplant recipients</topic><topic>Phenotype</topic><topic>Pulmonary arteries</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Spleen</topic><topic>Suppressor cells</topic><topic>Surgery</topic><topic>T cells</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - metabolism</topic><topic>Transplantation Immunology - genetics</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ge, Fangmin</creatorcontrib><creatorcontrib>Yuan, Shunzong</creatorcontrib><creatorcontrib>Su, Lida</creatorcontrib><creatorcontrib>Shen, Zhonghua</creatorcontrib><creatorcontrib>He, Aibin</creatorcontrib><creatorcontrib>Huang, Tao</creatorcontrib><creatorcontrib>Gong, Weihua</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 One Sustainability</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 - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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>Ge, Fangmin</au><au>Yuan, Shunzong</au><au>Su, Lida</au><au>Shen, Zhonghua</au><au>He, Aibin</au><au>Huang, Tao</au><au>Gong, Weihua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-10-16</date><risdate>2013</risdate><volume>8</volume><issue>10</issue><spage>e77559</spage><epage>e77559</epage><pages>e77559-e77559</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Engraftment of IL-6 deficient donor into wild-type recipient could significantly improve allograft survival through T cell lineage particularly regulatory T cells (Tregs) in non-sensitized transplant host. However, its effect on innate immune responses remains uncertain. Our data revealed that donor IL-6 deficiency significantly increased infiltration of two subsets of MDSCs (CD11b+Gr1+myeloid-derived suppressor cells), CD11b+Gr1(-low) and CD11b+Gr1(-int) with strong immunosuppression activity in the transplanted graft. It resulted in a dramatic increase of CD11b+Gr1(-low) frequency and a significant decrease of the frequency of CD11b+Gr1(-high) and CD4-CD8-NK1.1+ cells in the recipient's spleen. Unexpectedly, donor IL-6 deficiency could not significantly reduce macrophage frequency irrespective of in the host's spleen or graft. Taken together, suppression of innate immune effector cells and enhanced activity of regulatory MDSCs contributed to tolerance induction by blockade of IL-6 signaling pathway. The unveiled novel mechanism of targeting IL-6 might shed light on clinical therapeutic application in preventing accelerated allograft rejection for those pre-sensitized transplant recipients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24147024</pmid><doi>10.1371/journal.pone.0077559</doi><tpages>e77559</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-10, Vol.8 (10), p.e77559-e77559 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1442701952 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Allografts - immunology Allografts - metabolism Allografts - pathology Animals CD11b antigen CD11b Antigen - metabolism CD4 antigen CD8 antigen Cell lineage Cell survival Chemokines Coronary vessels Cytokines Data processing Effector cells Gene expression Graft rejection Graft Survival Health aspects Heart Heart Transplantation Immune response Immunity Immunity, Innate - genetics Immunological tolerance Immunophenotyping Immunoregulation Immunosuppression Immunotherapy Infiltration Innate immunity Interleukin 6 Interleukin-6 - deficiency Ischemia Lymphocytes Lymphocytes T Macrophages Male Medicine Mice Mice, Knockout Mitochondrial DNA Models, Animal Myeloid Cells - immunology Myeloid Cells - metabolism Myeloid Cells - pathology Organ transplant recipients Phenotype Pulmonary arteries Signal transduction Signaling Spleen Suppressor cells Surgery T cells T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Transplantation Immunology - genetics Transplants & implants |
| title | Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T19%3A37%3A51IST&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=Alteration%20of%20innate%20immunity%20by%20donor%20IL-6%20deficiency%20in%20a%20presensitized%20heart%20transplant%20model&rft.jtitle=PloS%20one&rft.au=Ge,%20Fangmin&rft.date=2013-10-16&rft.volume=8&rft.issue=10&rft.spage=e77559&rft.epage=e77559&rft.pages=e77559-e77559&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0077559&rft_dat=%3Cgale_plos_%3EA478246536%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=1442701952&rft_id=info:pmid/24147024&rft_galeid=A478246536&rft_doaj_id=oai_doaj_org_article_8f83f84911da4e4ab7cdfe35bbbada79&rfr_iscdi=true |