DC-SCRIPT Regulates IL-10 Production in Human Dendritic Cells by Modulating NF-κBp65 Activation
The balance between tolerance and immunity is important for the outcome of an infection or cancer, and dendritic cells (DCs) are key regulators of this balance. DC-specific transcript (DC-SCRIPT) is a protein expressed by DCs and has been demonstrated to suppress both TLR-mediated expression of IL-1...
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| Veröffentlicht in: | The Journal of immunology (1950) 2015-08, Vol.195 (4), p.1498-1505 |
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| container_title | The Journal of immunology (1950) |
| container_volume | 195 |
| creator | Søndergaard, Jonas Nørskov Poghosyan, Susanna Hontelez, Saartje Louche, Pauline Looman, Maaike W G Ansems, Marleen Adema, Gosse J |
| description | The balance between tolerance and immunity is important for the outcome of an infection or cancer, and dendritic cells (DCs) are key regulators of this balance. DC-specific transcript (DC-SCRIPT) is a protein expressed by DCs and has been demonstrated to suppress both TLR-mediated expression of IL-10 and glucocorticoid receptor-mediated transcription of glucocorticoid-induced leucine zipper (GILZ). Because GILZ is known to promote IL-10 production, we investigated whether these two processes are linked. Dual-knockdown and inhibition experiments demonstrated that neither GILZ nor glucocorticoid receptor play a role in TLR-induced IL-10 production after DC-SCRIPT knockdown. The NF-κB pathway is another route involved in IL-10 production after DC activation. Strikingly, inhibition of NF-κB led to a decreased TLR-mediated IL-10 production in DC-SCRIPT knockdown DCs. Moreover, DC-SCRIPT knockdown DCs showed enhanced phosphorylation, acetylation, and IL10 enhancer binding of the NF-κB subunit p65. These data demonstrate that besides nuclear receptor regulation, DC-SCRIPT also modulates activation of NF-κBp65 after TLR activation in human DCs. |
| doi_str_mv | 10.4049/jimmunol.1402924 |
| format | Article |
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DC-specific transcript (DC-SCRIPT) is a protein expressed by DCs and has been demonstrated to suppress both TLR-mediated expression of IL-10 and glucocorticoid receptor-mediated transcription of glucocorticoid-induced leucine zipper (GILZ). Because GILZ is known to promote IL-10 production, we investigated whether these two processes are linked. Dual-knockdown and inhibition experiments demonstrated that neither GILZ nor glucocorticoid receptor play a role in TLR-induced IL-10 production after DC-SCRIPT knockdown. The NF-κB pathway is another route involved in IL-10 production after DC activation. Strikingly, inhibition of NF-κB led to a decreased TLR-mediated IL-10 production in DC-SCRIPT knockdown DCs. Moreover, DC-SCRIPT knockdown DCs showed enhanced phosphorylation, acetylation, and IL10 enhancer binding of the NF-κB subunit p65. These data demonstrate that besides nuclear receptor regulation, DC-SCRIPT also modulates activation of NF-κBp65 after TLR activation in human DCs.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1402924</identifier><identifier>PMID: 26170389</identifier><language>eng</language><publisher>United States</publisher><subject>Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Enhancer Elements, Genetic ; Enzyme Activation ; Gene Knockout Techniques ; Humans ; Interleukin-10 - biosynthesis ; Interleukin-10 - genetics ; p300-CBP Transcription Factors - metabolism ; Phosphorylation ; Protein Binding ; Receptors, Glucocorticoid - metabolism ; RNA Interference ; Toll-Like Receptors - metabolism ; Transcription Factor RelA - metabolism ; Transcription Factors - metabolism</subject><ispartof>The Journal of immunology (1950), 2015-08, Vol.195 (4), p.1498-1505</ispartof><rights>Copyright © 2015 by The American Association of Immunologists, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c374t-73a1ca4e8c3119880150daf6e11b37ae6e46c00da264aaa764ad05ec9944c00b3</citedby><cites>FETCH-LOGICAL-c374t-73a1ca4e8c3119880150daf6e11b37ae6e46c00da264aaa764ad05ec9944c00b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26170389$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Søndergaard, Jonas Nørskov</creatorcontrib><creatorcontrib>Poghosyan, Susanna</creatorcontrib><creatorcontrib>Hontelez, Saartje</creatorcontrib><creatorcontrib>Louche, Pauline</creatorcontrib><creatorcontrib>Looman, Maaike W G</creatorcontrib><creatorcontrib>Ansems, Marleen</creatorcontrib><creatorcontrib>Adema, Gosse J</creatorcontrib><title>DC-SCRIPT Regulates IL-10 Production in Human Dendritic Cells by Modulating NF-κBp65 Activation</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>The balance between tolerance and immunity is important for the outcome of an infection or cancer, and dendritic cells (DCs) are key regulators of this balance. DC-specific transcript (DC-SCRIPT) is a protein expressed by DCs and has been demonstrated to suppress both TLR-mediated expression of IL-10 and glucocorticoid receptor-mediated transcription of glucocorticoid-induced leucine zipper (GILZ). Because GILZ is known to promote IL-10 production, we investigated whether these two processes are linked. Dual-knockdown and inhibition experiments demonstrated that neither GILZ nor glucocorticoid receptor play a role in TLR-induced IL-10 production after DC-SCRIPT knockdown. The NF-κB pathway is another route involved in IL-10 production after DC activation. Strikingly, inhibition of NF-κB led to a decreased TLR-mediated IL-10 production in DC-SCRIPT knockdown DCs. Moreover, DC-SCRIPT knockdown DCs showed enhanced phosphorylation, acetylation, and IL10 enhancer binding of the NF-κB subunit p65. These data demonstrate that besides nuclear receptor regulation, DC-SCRIPT also modulates activation of NF-κBp65 after TLR activation in human DCs.</description><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Enhancer Elements, Genetic</subject><subject>Enzyme Activation</subject><subject>Gene Knockout Techniques</subject><subject>Humans</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Interleukin-10 - genetics</subject><subject>p300-CBP Transcription Factors - metabolism</subject><subject>Phosphorylation</subject><subject>Protein Binding</subject><subject>Receptors, Glucocorticoid - metabolism</subject><subject>RNA Interference</subject><subject>Toll-Like Receptors - metabolism</subject><subject>Transcription Factor RelA - metabolism</subject><subject>Transcription Factors - metabolism</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>eNqFkc1OAjEUhRujEUT3rkyXboq3nU47s9RBhASVIK7H0imkZH5wOmPCq_kQPpMlgFs39yYn5zu5uQehawp9Djy-W9uiaMsq71MOLGb8BHVpGAIRAsQp6gIwRqgUsoMunFsDgADGz1GHCSohiOIu-hgk5C2ZjadzPDOrNleNcXg8IRTwtK6yVje2KrEt8agtVIkHpsxq21iNE5PnDi-2-Nm7PGbLFX4Zkp_vh40I8b3nvtSOvURnS5U7c3XYPfQ-fJwnIzJ5fRon9xOiA8kbIgNFteIm0gGlcRQBDSFTS2EoXQRSGWG40OAlJrhSSvqZQWh0HHPu9UXQQ7f73E1dfbbGNWlhnfZHqtJUrUtpBJGQMgjp_1YJTISMi50V9lZdV87VZplualuoeptSSHcVpMcK0kMFHrk5pLeLwmR_wPHnwS-XpIId</recordid><startdate>20150815</startdate><enddate>20150815</enddate><creator>Søndergaard, Jonas Nørskov</creator><creator>Poghosyan, Susanna</creator><creator>Hontelez, Saartje</creator><creator>Louche, Pauline</creator><creator>Looman, Maaike W G</creator><creator>Ansems, Marleen</creator><creator>Adema, Gosse J</creator><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></search><sort><creationdate>20150815</creationdate><title>DC-SCRIPT Regulates IL-10 Production in Human Dendritic Cells by Modulating NF-κBp65 Activation</title><author>Søndergaard, Jonas Nørskov ; Poghosyan, Susanna ; Hontelez, Saartje ; Louche, Pauline ; Looman, Maaike W G ; Ansems, Marleen ; Adema, Gosse J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-73a1ca4e8c3119880150daf6e11b37ae6e46c00da264aaa764ad05ec9944c00b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Enhancer Elements, Genetic</topic><topic>Enzyme Activation</topic><topic>Gene Knockout Techniques</topic><topic>Humans</topic><topic>Interleukin-10 - biosynthesis</topic><topic>Interleukin-10 - genetics</topic><topic>p300-CBP Transcription Factors - metabolism</topic><topic>Phosphorylation</topic><topic>Protein Binding</topic><topic>Receptors, Glucocorticoid - metabolism</topic><topic>RNA Interference</topic><topic>Toll-Like Receptors - metabolism</topic><topic>Transcription Factor RelA - metabolism</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Søndergaard, Jonas Nørskov</creatorcontrib><creatorcontrib>Poghosyan, Susanna</creatorcontrib><creatorcontrib>Hontelez, Saartje</creatorcontrib><creatorcontrib>Louche, Pauline</creatorcontrib><creatorcontrib>Looman, Maaike W G</creatorcontrib><creatorcontrib>Ansems, Marleen</creatorcontrib><creatorcontrib>Adema, Gosse J</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><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Søndergaard, Jonas Nørskov</au><au>Poghosyan, Susanna</au><au>Hontelez, Saartje</au><au>Louche, Pauline</au><au>Looman, Maaike W G</au><au>Ansems, Marleen</au><au>Adema, Gosse J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DC-SCRIPT Regulates IL-10 Production in Human Dendritic Cells by Modulating NF-κBp65 Activation</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2015-08-15</date><risdate>2015</risdate><volume>195</volume><issue>4</issue><spage>1498</spage><epage>1505</epage><pages>1498-1505</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>The balance between tolerance and immunity is important for the outcome of an infection or cancer, and dendritic cells (DCs) are key regulators of this balance. DC-specific transcript (DC-SCRIPT) is a protein expressed by DCs and has been demonstrated to suppress both TLR-mediated expression of IL-10 and glucocorticoid receptor-mediated transcription of glucocorticoid-induced leucine zipper (GILZ). Because GILZ is known to promote IL-10 production, we investigated whether these two processes are linked. Dual-knockdown and inhibition experiments demonstrated that neither GILZ nor glucocorticoid receptor play a role in TLR-induced IL-10 production after DC-SCRIPT knockdown. The NF-κB pathway is another route involved in IL-10 production after DC activation. Strikingly, inhibition of NF-κB led to a decreased TLR-mediated IL-10 production in DC-SCRIPT knockdown DCs. Moreover, DC-SCRIPT knockdown DCs showed enhanced phosphorylation, acetylation, and IL10 enhancer binding of the NF-κB subunit p65. These data demonstrate that besides nuclear receptor regulation, DC-SCRIPT also modulates activation of NF-κBp65 after TLR activation in human DCs.</abstract><cop>United States</cop><pmid>26170389</pmid><doi>10.4049/jimmunol.1402924</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Carrier Proteins - genetics Carrier Proteins - metabolism Dendritic Cells - immunology Dendritic Cells - metabolism Enhancer Elements, Genetic Enzyme Activation Gene Knockout Techniques Humans Interleukin-10 - biosynthesis Interleukin-10 - genetics p300-CBP Transcription Factors - metabolism Phosphorylation Protein Binding Receptors, Glucocorticoid - metabolism RNA Interference Toll-Like Receptors - metabolism Transcription Factor RelA - metabolism Transcription Factors - metabolism |
| title | DC-SCRIPT Regulates IL-10 Production in Human Dendritic Cells by Modulating NF-κBp65 Activation |
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