Engulfment of activated apoptotic cells abolishes TGF-β-mediated immunoregulation via the induction of IL-6
Phagocytosis of apoptotic cells (ACs) is usually a potent immunoregulatory signal but can also promote inflammation. In this article, we show that administration of apoptotic dendritic cells (DCs) inhibited inflammation in vivo through increasing production of TGF-β from intrinsic DCs and B cells. H...
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| Veröffentlicht in: | The Journal of immunology (1950) 2015-02, Vol.194 (4), p.1621-1627 |
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| container_issue | 4 |
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| container_title | The Journal of immunology (1950) |
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| creator | Notley, Clare A Brown, Mark A McGovern, Jenny L Jordan, Christine K Ehrenstein, Michael R |
| description | Phagocytosis of apoptotic cells (ACs) is usually a potent immunoregulatory signal but can also promote inflammation. In this article, we show that administration of apoptotic dendritic cells (DCs) inhibited inflammation in vivo through increasing production of TGF-β from intrinsic DCs and B cells. However, ACs derived from LPS-activated DCs failed to restrain inflammation because of a short-lived but marked IL-6 response, which abolished the increase in TGF-β. Inhibition of IL-6 restored the protective anti-inflammatory properties of aACs and the TGF-β response. DCs isolated from mice that had received resting but not activated ACs could transfer the suppression of inflammation to recipient mice. These transferred DCs stimulated B cell TGF-β production and relied on an intact B cell compartment to limit inflammation. These results highlight how the activation state of AC governs their ability to control inflammation through reciprocal regulation of IL-6 and TGF-β. |
| doi_str_mv | 10.4049/jimmunol.1401256 |
| format | Article |
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In this article, we show that administration of apoptotic dendritic cells (DCs) inhibited inflammation in vivo through increasing production of TGF-β from intrinsic DCs and B cells. However, ACs derived from LPS-activated DCs failed to restrain inflammation because of a short-lived but marked IL-6 response, which abolished the increase in TGF-β. Inhibition of IL-6 restored the protective anti-inflammatory properties of aACs and the TGF-β response. DCs isolated from mice that had received resting but not activated ACs could transfer the suppression of inflammation to recipient mice. These transferred DCs stimulated B cell TGF-β production and relied on an intact B cell compartment to limit inflammation. These results highlight how the activation state of AC governs their ability to control inflammation through reciprocal regulation of IL-6 and TGF-β.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1401256</identifier><identifier>PMID: 25601923</identifier><language>eng</language><publisher>United States: AAI</publisher><subject>Animals ; Apoptosis - immunology ; Arthritis, Experimental ; Dendritic Cells - immunology ; Flow Cytometry ; Immune Regulation ; Inflammation - immunology ; Interleukin-6 - biosynthesis ; Interleukin-6 - immunology ; Macrophages - immunology ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Phagocytosis - immunology ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta - immunology</subject><ispartof>The Journal of immunology (1950), 2015-02, Vol.194 (4), p.1621-1627</ispartof><rights>Copyright © 2015 The Authors.</rights><rights>Copyright © 2015 The Authors 2015 Copyright © 2015 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-360b2f4bfc968e147d96dd1f4682cb08157be6a9e650ba1e03e4e3eed2c3b0763</citedby><cites>FETCH-LOGICAL-c429t-360b2f4bfc968e147d96dd1f4682cb08157be6a9e650ba1e03e4e3eed2c3b0763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25601923$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Notley, Clare A</creatorcontrib><creatorcontrib>Brown, Mark A</creatorcontrib><creatorcontrib>McGovern, Jenny L</creatorcontrib><creatorcontrib>Jordan, Christine K</creatorcontrib><creatorcontrib>Ehrenstein, Michael R</creatorcontrib><title>Engulfment of activated apoptotic cells abolishes TGF-β-mediated immunoregulation via the induction of IL-6</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Phagocytosis of apoptotic cells (ACs) is usually a potent immunoregulatory signal but can also promote inflammation. In this article, we show that administration of apoptotic dendritic cells (DCs) inhibited inflammation in vivo through increasing production of TGF-β from intrinsic DCs and B cells. However, ACs derived from LPS-activated DCs failed to restrain inflammation because of a short-lived but marked IL-6 response, which abolished the increase in TGF-β. Inhibition of IL-6 restored the protective anti-inflammatory properties of aACs and the TGF-β response. DCs isolated from mice that had received resting but not activated ACs could transfer the suppression of inflammation to recipient mice. These transferred DCs stimulated B cell TGF-β production and relied on an intact B cell compartment to limit inflammation. These results highlight how the activation state of AC governs their ability to control inflammation through reciprocal regulation of IL-6 and TGF-β.</description><subject>Animals</subject><subject>Apoptosis - immunology</subject><subject>Arthritis, Experimental</subject><subject>Dendritic Cells - immunology</subject><subject>Flow Cytometry</subject><subject>Immune Regulation</subject><subject>Inflammation - immunology</subject><subject>Interleukin-6 - biosynthesis</subject><subject>Interleukin-6 - immunology</subject><subject>Macrophages - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy, Confocal</subject><subject>Phagocytosis - immunology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Transforming Growth Factor beta - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctq3DAUhkVoaSZp91kVLbtxenTxsb0plJAbDHSTroUsH2cUbGtqyQN9rT5InylKZhKaVVcC6T8f_9HH2JmAcw26-frgx3GZwnAuNAhZ4hFbibKEAhHwHVsBSFmICqtjdhLjAwAgSP2BHecoiEaqFRsup_tl6EeaEg89ty75nU3UcbsN2xSSd9zRMERu2zD4uKHI766vir9_ipE6_5zcd5gpc2zyYeI7b3naEPdTt7jnm0y-XRf4kb3v7RDp0-E8ZT-vLu8ubor1j-vbi-_rwmnZpEIhtLLXbe8arEnoqmuw60SvsZauhVqUVUtoG8ISWisIFGlSRJ10qoUK1Sn7tudulzbXdHm52Q5mO_vRzr9NsN68fZn8xtyHndFKNEpABnw5AObwa6GYzOjj0z_YicISjaihRlGBVP-PYqmyGoE6R2EfdXOIcab-tZEA8-TTvPg0B5955PO_m7wOvAhUj3_UoKU</recordid><startdate>20150215</startdate><enddate>20150215</enddate><creator>Notley, Clare A</creator><creator>Brown, Mark A</creator><creator>McGovern, Jenny L</creator><creator>Jordan, Christine K</creator><creator>Ehrenstein, Michael R</creator><general>AAI</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>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20150215</creationdate><title>Engulfment of activated apoptotic cells abolishes TGF-β-mediated immunoregulation via the induction of IL-6</title><author>Notley, Clare A ; Brown, Mark A ; McGovern, Jenny L ; Jordan, Christine K ; Ehrenstein, Michael R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-360b2f4bfc968e147d96dd1f4682cb08157be6a9e650ba1e03e4e3eed2c3b0763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Apoptosis - immunology</topic><topic>Arthritis, Experimental</topic><topic>Dendritic Cells - immunology</topic><topic>Flow Cytometry</topic><topic>Immune Regulation</topic><topic>Inflammation - immunology</topic><topic>Interleukin-6 - biosynthesis</topic><topic>Interleukin-6 - immunology</topic><topic>Macrophages - immunology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy, Confocal</topic><topic>Phagocytosis - immunology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Transforming Growth Factor beta - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Notley, Clare A</creatorcontrib><creatorcontrib>Brown, Mark A</creatorcontrib><creatorcontrib>McGovern, Jenny L</creatorcontrib><creatorcontrib>Jordan, Christine K</creatorcontrib><creatorcontrib>Ehrenstein, Michael R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Notley, Clare A</au><au>Brown, Mark A</au><au>McGovern, Jenny L</au><au>Jordan, Christine K</au><au>Ehrenstein, Michael R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Engulfment of activated apoptotic cells abolishes TGF-β-mediated immunoregulation via the induction of IL-6</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2015-02-15</date><risdate>2015</risdate><volume>194</volume><issue>4</issue><spage>1621</spage><epage>1627</epage><pages>1621-1627</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Phagocytosis of apoptotic cells (ACs) is usually a potent immunoregulatory signal but can also promote inflammation. 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These results highlight how the activation state of AC governs their ability to control inflammation through reciprocal regulation of IL-6 and TGF-β.</abstract><cop>United States</cop><pub>AAI</pub><pmid>25601923</pmid><doi>10.4049/jimmunol.1401256</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0022-1767 1550-6606 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Apoptosis - immunology Arthritis, Experimental Dendritic Cells - immunology Flow Cytometry Immune Regulation Inflammation - immunology Interleukin-6 - biosynthesis Interleukin-6 - immunology Macrophages - immunology Mice Mice, Inbred C57BL Microscopy, Confocal Phagocytosis - immunology Reverse Transcriptase Polymerase Chain Reaction Transforming Growth Factor beta - immunology |
| title | Engulfment of activated apoptotic cells abolishes TGF-β-mediated immunoregulation via the induction of IL-6 |
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