The high affinity IgE receptor: a signaling update
•Differences in affinity, valency, concentration of FcεRI-aggregating ligands are translated into distinct signaling outcomes.•Mast cell degranulation implicates a highly complex molecular machinery regulating granule transport and membrane fusion.•Advances made in signaling-dependent cytokine and c...
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Veröffentlicht in: | Current opinion in immunology 2021-10, Vol.72, p.51-58 |
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creator | Blank, Ulrich Huang, Hua Kawakami, Toshiaki |
description | •Differences in affinity, valency, concentration of FcεRI-aggregating ligands are translated into distinct signaling outcomes.•Mast cell degranulation implicates a highly complex molecular machinery regulating granule transport and membrane fusion.•Advances made in signaling-dependent cytokine and chemokine gene transcription in response to antigenic stimulation.
Here we update receptor proximal and distant signaling events of the mast cell high affinity IgE receptor (FcεRI) launching immediate type I hypersensitivity and an inflammatory cytokine-chemokine cascade. Different physiologic antigen concentrations, their affinity, and valency for the IgE ligand produce distinct intracellular signaling events with different outcomes. Investigating mast cell degranulation has revealed a complex molecular machinery that relays proximal signaling to cytoskeletal reorganization, granule transport and membrane fusion. Several new phosphorylation- and calcium-responsive effectors have been described. FcεRI signaling also promotes de novo gene transcription. Recent progress has identified enhancers at genes that are upregulated in mast cells after stimulation through FcεRI using next generation sequencing methods. Enhancers at genes that respond to antigenic stimulation in human mast cells revealed Ca2+-dependency. Stimulation-responsive super enhancers in mouse mast cells have also been identified. Mast cell lineage-determining transcription factor GATA2 primes these enhancers to respond to antigenic stimulation. |
doi_str_mv | 10.1016/j.coi.2021.03.015 |
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Here we update receptor proximal and distant signaling events of the mast cell high affinity IgE receptor (FcεRI) launching immediate type I hypersensitivity and an inflammatory cytokine-chemokine cascade. Different physiologic antigen concentrations, their affinity, and valency for the IgE ligand produce distinct intracellular signaling events with different outcomes. Investigating mast cell degranulation has revealed a complex molecular machinery that relays proximal signaling to cytoskeletal reorganization, granule transport and membrane fusion. Several new phosphorylation- and calcium-responsive effectors have been described. FcεRI signaling also promotes de novo gene transcription. Recent progress has identified enhancers at genes that are upregulated in mast cells after stimulation through FcεRI using next generation sequencing methods. Enhancers at genes that respond to antigenic stimulation in human mast cells revealed Ca2+-dependency. Stimulation-responsive super enhancers in mouse mast cells have also been identified. Mast cell lineage-determining transcription factor GATA2 primes these enhancers to respond to antigenic stimulation.</description><identifier>ISSN: 0952-7915</identifier><identifier>EISSN: 1879-0372</identifier><identifier>DOI: 10.1016/j.coi.2021.03.015</identifier><identifier>PMID: 33838574</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antigens - immunology ; Cell Degranulation - immunology ; Cytokines - genetics ; Cytokines - metabolism ; Exocytosis - immunology ; Gene Expression Regulation ; Humans ; Immunity ; Immunoglobulin E - immunology ; Immunomodulation ; Life Sciences ; Protein Binding ; Receptors, IgE - metabolism ; Signal Transduction</subject><ispartof>Current opinion in immunology, 2021-10, Vol.72, p.51-58</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-48df93d816108256feeb749d3e76799d500d6fdc32b91b7e6dc1d1c8b4218093</citedby><cites>FETCH-LOGICAL-c496t-48df93d816108256feeb749d3e76799d500d6fdc32b91b7e6dc1d1c8b4218093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.coi.2021.03.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33838574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03406061$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Blank, Ulrich</creatorcontrib><creatorcontrib>Huang, Hua</creatorcontrib><creatorcontrib>Kawakami, Toshiaki</creatorcontrib><title>The high affinity IgE receptor: a signaling update</title><title>Current opinion in immunology</title><addtitle>Curr Opin Immunol</addtitle><description>•Differences in affinity, valency, concentration of FcεRI-aggregating ligands are translated into distinct signaling outcomes.•Mast cell degranulation implicates a highly complex molecular machinery regulating granule transport and membrane fusion.•Advances made in signaling-dependent cytokine and chemokine gene transcription in response to antigenic stimulation.
Here we update receptor proximal and distant signaling events of the mast cell high affinity IgE receptor (FcεRI) launching immediate type I hypersensitivity and an inflammatory cytokine-chemokine cascade. Different physiologic antigen concentrations, their affinity, and valency for the IgE ligand produce distinct intracellular signaling events with different outcomes. Investigating mast cell degranulation has revealed a complex molecular machinery that relays proximal signaling to cytoskeletal reorganization, granule transport and membrane fusion. Several new phosphorylation- and calcium-responsive effectors have been described. FcεRI signaling also promotes de novo gene transcription. Recent progress has identified enhancers at genes that are upregulated in mast cells after stimulation through FcεRI using next generation sequencing methods. Enhancers at genes that respond to antigenic stimulation in human mast cells revealed Ca2+-dependency. Stimulation-responsive super enhancers in mouse mast cells have also been identified. Mast cell lineage-determining transcription factor GATA2 primes these enhancers to respond to antigenic stimulation.</description><subject>Animals</subject><subject>Antigens - immunology</subject><subject>Cell Degranulation - immunology</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Exocytosis - immunology</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Immunity</subject><subject>Immunoglobulin E - immunology</subject><subject>Immunomodulation</subject><subject>Life Sciences</subject><subject>Protein Binding</subject><subject>Receptors, IgE - metabolism</subject><subject>Signal Transduction</subject><issn>0952-7915</issn><issn>1879-0372</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMGK2zAQQEXZ0k23_YBeFh-3B7szkiVb7SmEtAkEesldyNI4UXDsrOUs5O9XIdu99TQwvHkDj7FvCAUCqh-Hwg2h4MCxAFEAyg9shnWlcxAVv2Mz0JLnlUZ5zz7HeAAAKQV8YvdC1KKWVTljfLunbB92-8y2bejDdMnWu2U2kqPTNIw_M5vFsOttF_pddj55O9EX9rG1XaSvb_OBbX8vt4tVvvn7Z72Yb3JXajXlZe1bLXyNCqHmUrVETVVqL6hSldZeAnjVeid4o7GpSHmHHl3dlBxr0OKBfb9p97YzpzEc7Xgxgw1mNd-Y6w5ECQoUvmBin27saRyezxQncwzRUdfZnoZzNFwi8hLTSCjeUDcOMY7UvrsRzLWqOZhU1VyrphcmVU03j2_6c3Mk_37xL2MCft0ASj1eAo0mukC9Ix9Sycn4JPy__hU47oSA</recordid><startdate>202110</startdate><enddate>202110</enddate><creator>Blank, Ulrich</creator><creator>Huang, Hua</creator><creator>Kawakami, Toshiaki</creator><general>Elsevier Ltd</general><general>Elsevier</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>1XC</scope><scope>VOOES</scope></search><sort><creationdate>202110</creationdate><title>The high affinity IgE receptor: a signaling update</title><author>Blank, Ulrich ; Huang, Hua ; Kawakami, Toshiaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-48df93d816108256feeb749d3e76799d500d6fdc32b91b7e6dc1d1c8b4218093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antigens - immunology</topic><topic>Cell Degranulation - immunology</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>Exocytosis - immunology</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Immunity</topic><topic>Immunoglobulin E - immunology</topic><topic>Immunomodulation</topic><topic>Life Sciences</topic><topic>Protein Binding</topic><topic>Receptors, IgE - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Blank, Ulrich</creatorcontrib><creatorcontrib>Huang, Hua</creatorcontrib><creatorcontrib>Kawakami, Toshiaki</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>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Current opinion in immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Blank, Ulrich</au><au>Huang, Hua</au><au>Kawakami, Toshiaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The high affinity IgE receptor: a signaling update</atitle><jtitle>Current opinion in immunology</jtitle><addtitle>Curr Opin Immunol</addtitle><date>2021-10</date><risdate>2021</risdate><volume>72</volume><spage>51</spage><epage>58</epage><pages>51-58</pages><issn>0952-7915</issn><eissn>1879-0372</eissn><abstract>•Differences in affinity, valency, concentration of FcεRI-aggregating ligands are translated into distinct signaling outcomes.•Mast cell degranulation implicates a highly complex molecular machinery regulating granule transport and membrane fusion.•Advances made in signaling-dependent cytokine and chemokine gene transcription in response to antigenic stimulation.
Here we update receptor proximal and distant signaling events of the mast cell high affinity IgE receptor (FcεRI) launching immediate type I hypersensitivity and an inflammatory cytokine-chemokine cascade. Different physiologic antigen concentrations, their affinity, and valency for the IgE ligand produce distinct intracellular signaling events with different outcomes. Investigating mast cell degranulation has revealed a complex molecular machinery that relays proximal signaling to cytoskeletal reorganization, granule transport and membrane fusion. Several new phosphorylation- and calcium-responsive effectors have been described. FcεRI signaling also promotes de novo gene transcription. Recent progress has identified enhancers at genes that are upregulated in mast cells after stimulation through FcεRI using next generation sequencing methods. Enhancers at genes that respond to antigenic stimulation in human mast cells revealed Ca2+-dependency. Stimulation-responsive super enhancers in mouse mast cells have also been identified. Mast cell lineage-determining transcription factor GATA2 primes these enhancers to respond to antigenic stimulation.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33838574</pmid><doi>10.1016/j.coi.2021.03.015</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antigens - immunology Cell Degranulation - immunology Cytokines - genetics Cytokines - metabolism Exocytosis - immunology Gene Expression Regulation Humans Immunity Immunoglobulin E - immunology Immunomodulation Life Sciences Protein Binding Receptors, IgE - metabolism Signal Transduction |
title | The high affinity IgE receptor: a signaling update |
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