Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKK[epsilon]- and CYLD-dependent Bcl3 activation
Carbohydrate-specific signalling through DC-SIGN provides dendritic cells with plasticity to tailor immunity to the nature of invading microbes. Here we demonstrate that recognition of fucose-expressing extracellular pathogens like Schistosoma mansoni and Helicobacter pylori by DC-SIGN favors T help...
Gespeichert in:
| Veröffentlicht in: | Nature communications 2014-05, Vol.5, p.3898 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | |
| container_start_page | 3898 |
| container_title | Nature communications |
| container_volume | 5 |
| creator | Gringhuis, Sonja I Kaptein, Tanja M Wevers, Brigitte A Mesman, Annelies W Geijtenbeek, Teunis B H |
| description | Carbohydrate-specific signalling through DC-SIGN provides dendritic cells with plasticity to tailor immunity to the nature of invading microbes. Here we demonstrate that recognition of fucose-expressing extracellular pathogens like Schistosoma mansoni and Helicobacter pylori by DC-SIGN favors T helper cell type-2 (TH 2) responses via activation of atypical NF-κB family member Bcl3. Crosstalk between TLR and DC-SIGN signalling results in TLR-induced MK2-mediated phosphorylation of LSP1, associated with DC-SIGN, upon fucose binding. Subsequently, IKK[straight epsilon] and CYLD are recruited to phosphorylated LSP1. IKK[straight epsilon] activation is pivotal for suppression of CYLD deubiquitinase activity and subsequent nuclear translocation of ubiquitinated Bcl3. Bcl3 activation represses TLR-induced proinflammatory cytokine expression, while enhancing interleukin-10 (IL-10) and TH 2-attracting chemokine expression, shifting TH differentiation from TH 1 to TH 2 polarization. Thus, DC-SIGN directs adaptive TH 2 immunity to fucose-expressing pathogens via an IKK[straight epsilon]-CYLD-dependent signalling pathway leading to Bcl3 activation, which might be targeted in vaccination strategies or to prevent aberrant inflammation and allergy. |
| doi_str_mv | 10.1038/ncomms4898 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_journals_1528939920</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3316554031</sourcerecordid><originalsourceid>FETCH-proquest_journals_15289399203</originalsourceid><addsrcrecordid>eNqNjr1KQzEYQIMgWLSLT_CBczQ_V0xWb62WiotdRKSE3K81JU1ivtyCi89uBx_As5zlDIexSymupdDmJvm831NnrDlhEyU6yeWd0mdsSrQTR7SVpusm7Gc--kzIqaAPm-Bh1vPXxeMLUNgmF2NIWxhCRd8IVvCJsWAFjzFC-y7IFVSkkhMhwSE4WCyX71goxJw-OLg0QP_2POMDFkwDpgb3PmpwvoWDayGnC3a6cZFw-udzdjV_WPVPvNT8NSK19S6P9ThCa3mrjNXWKqH_V_0CU8hTJA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1528939920</pqid></control><display><type>article</type><title>Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKK[epsilon]- and CYLD-dependent Bcl3 activation</title><source>Nature Free</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Springer Nature OA Free Journals</source><creator>Gringhuis, Sonja I ; Kaptein, Tanja M ; Wevers, Brigitte A ; Mesman, Annelies W ; Geijtenbeek, Teunis B H</creator><creatorcontrib>Gringhuis, Sonja I ; Kaptein, Tanja M ; Wevers, Brigitte A ; Mesman, Annelies W ; Geijtenbeek, Teunis B H</creatorcontrib><description>Carbohydrate-specific signalling through DC-SIGN provides dendritic cells with plasticity to tailor immunity to the nature of invading microbes. Here we demonstrate that recognition of fucose-expressing extracellular pathogens like Schistosoma mansoni and Helicobacter pylori by DC-SIGN favors T helper cell type-2 (TH 2) responses via activation of atypical NF-κB family member Bcl3. Crosstalk between TLR and DC-SIGN signalling results in TLR-induced MK2-mediated phosphorylation of LSP1, associated with DC-SIGN, upon fucose binding. Subsequently, IKK[straight epsilon] and CYLD are recruited to phosphorylated LSP1. IKK[straight epsilon] activation is pivotal for suppression of CYLD deubiquitinase activity and subsequent nuclear translocation of ubiquitinated Bcl3. Bcl3 activation represses TLR-induced proinflammatory cytokine expression, while enhancing interleukin-10 (IL-10) and TH 2-attracting chemokine expression, shifting TH differentiation from TH 1 to TH 2 polarization. Thus, DC-SIGN directs adaptive TH 2 immunity to fucose-expressing pathogens via an IKK[straight epsilon]-CYLD-dependent signalling pathway leading to Bcl3 activation, which might be targeted in vaccination strategies or to prevent aberrant inflammation and allergy.</description><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms4898</identifier><language>eng</language><publisher>London: Nature Publishing Group</publisher><subject>Cytokines ; Dendritic cells ; Kinases ; Pathogens ; Phosphorylation</subject><ispartof>Nature communications, 2014-05, Vol.5, p.3898</ispartof><rights>Copyright Nature Publishing Group May 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></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></links><search><creatorcontrib>Gringhuis, Sonja I</creatorcontrib><creatorcontrib>Kaptein, Tanja M</creatorcontrib><creatorcontrib>Wevers, Brigitte A</creatorcontrib><creatorcontrib>Mesman, Annelies W</creatorcontrib><creatorcontrib>Geijtenbeek, Teunis B H</creatorcontrib><title>Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKK[epsilon]- and CYLD-dependent Bcl3 activation</title><title>Nature communications</title><description>Carbohydrate-specific signalling through DC-SIGN provides dendritic cells with plasticity to tailor immunity to the nature of invading microbes. Here we demonstrate that recognition of fucose-expressing extracellular pathogens like Schistosoma mansoni and Helicobacter pylori by DC-SIGN favors T helper cell type-2 (TH 2) responses via activation of atypical NF-κB family member Bcl3. Crosstalk between TLR and DC-SIGN signalling results in TLR-induced MK2-mediated phosphorylation of LSP1, associated with DC-SIGN, upon fucose binding. Subsequently, IKK[straight epsilon] and CYLD are recruited to phosphorylated LSP1. IKK[straight epsilon] activation is pivotal for suppression of CYLD deubiquitinase activity and subsequent nuclear translocation of ubiquitinated Bcl3. Bcl3 activation represses TLR-induced proinflammatory cytokine expression, while enhancing interleukin-10 (IL-10) and TH 2-attracting chemokine expression, shifting TH differentiation from TH 1 to TH 2 polarization. Thus, DC-SIGN directs adaptive TH 2 immunity to fucose-expressing pathogens via an IKK[straight epsilon]-CYLD-dependent signalling pathway leading to Bcl3 activation, which might be targeted in vaccination strategies or to prevent aberrant inflammation and allergy.</description><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Kinases</subject><subject>Pathogens</subject><subject>Phosphorylation</subject><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNqNjr1KQzEYQIMgWLSLT_CBczQ_V0xWb62WiotdRKSE3K81JU1ivtyCi89uBx_As5zlDIexSymupdDmJvm831NnrDlhEyU6yeWd0mdsSrQTR7SVpusm7Gc--kzIqaAPm-Bh1vPXxeMLUNgmF2NIWxhCRd8IVvCJsWAFjzFC-y7IFVSkkhMhwSE4WCyX71goxJw-OLg0QP_2POMDFkwDpgb3PmpwvoWDayGnC3a6cZFw-udzdjV_WPVPvNT8NSK19S6P9ThCa3mrjNXWKqH_V_0CU8hTJA</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Gringhuis, Sonja I</creator><creator>Kaptein, Tanja M</creator><creator>Wevers, Brigitte A</creator><creator>Mesman, Annelies W</creator><creator>Geijtenbeek, Teunis B H</creator><general>Nature Publishing Group</general><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>SOI</scope></search><sort><creationdate>20140501</creationdate><title>Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKK[epsilon]- and CYLD-dependent Bcl3 activation</title><author>Gringhuis, Sonja I ; Kaptein, Tanja M ; Wevers, Brigitte A ; Mesman, Annelies W ; Geijtenbeek, Teunis B H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_15289399203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Cytokines</topic><topic>Dendritic cells</topic><topic>Kinases</topic><topic>Pathogens</topic><topic>Phosphorylation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gringhuis, Sonja I</creatorcontrib><creatorcontrib>Kaptein, Tanja M</creatorcontrib><creatorcontrib>Wevers, Brigitte A</creatorcontrib><creatorcontrib>Mesman, Annelies W</creatorcontrib><creatorcontrib>Geijtenbeek, Teunis B H</creatorcontrib><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</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>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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace 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 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>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>Environment Abstracts</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gringhuis, Sonja I</au><au>Kaptein, Tanja M</au><au>Wevers, Brigitte A</au><au>Mesman, Annelies W</au><au>Geijtenbeek, Teunis B H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKK[epsilon]- and CYLD-dependent Bcl3 activation</atitle><jtitle>Nature communications</jtitle><date>2014-05-01</date><risdate>2014</risdate><volume>5</volume><spage>3898</spage><pages>3898-</pages><eissn>2041-1723</eissn><abstract>Carbohydrate-specific signalling through DC-SIGN provides dendritic cells with plasticity to tailor immunity to the nature of invading microbes. Here we demonstrate that recognition of fucose-expressing extracellular pathogens like Schistosoma mansoni and Helicobacter pylori by DC-SIGN favors T helper cell type-2 (TH 2) responses via activation of atypical NF-κB family member Bcl3. Crosstalk between TLR and DC-SIGN signalling results in TLR-induced MK2-mediated phosphorylation of LSP1, associated with DC-SIGN, upon fucose binding. Subsequently, IKK[straight epsilon] and CYLD are recruited to phosphorylated LSP1. IKK[straight epsilon] activation is pivotal for suppression of CYLD deubiquitinase activity and subsequent nuclear translocation of ubiquitinated Bcl3. Bcl3 activation represses TLR-induced proinflammatory cytokine expression, while enhancing interleukin-10 (IL-10) and TH 2-attracting chemokine expression, shifting TH differentiation from TH 1 to TH 2 polarization. Thus, DC-SIGN directs adaptive TH 2 immunity to fucose-expressing pathogens via an IKK[straight epsilon]-CYLD-dependent signalling pathway leading to Bcl3 activation, which might be targeted in vaccination strategies or to prevent aberrant inflammation and allergy.</abstract><cop>London</cop><pub>Nature Publishing Group</pub><doi>10.1038/ncomms4898</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | EISSN: 2041-1723 |
| ispartof | Nature communications, 2014-05, Vol.5, p.3898 |
| issn | 2041-1723 |
| language | eng |
| recordid | cdi_proquest_journals_1528939920 |
| source | Nature Free; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Springer Nature OA Free Journals |
| subjects | Cytokines Dendritic cells Kinases Pathogens Phosphorylation |
| title | Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKK[epsilon]- and CYLD-dependent Bcl3 activation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T02%3A06%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fucose-specific%20DC-SIGN%20signalling%20directs%20T%20helper%20cell%20type-2%20responses%20via%20IKK%5Bepsilon%5D-%20and%20CYLD-dependent%20Bcl3%20activation&rft.jtitle=Nature%20communications&rft.au=Gringhuis,%20Sonja%20I&rft.date=2014-05-01&rft.volume=5&rft.spage=3898&rft.pages=3898-&rft.eissn=2041-1723&rft_id=info:doi/10.1038/ncomms4898&rft_dat=%3Cproquest%3E3316554031%3C/proquest%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1528939920&rft_id=info:pmid/&rfr_iscdi=true |