Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ T(H)2 cells
Mouse CCL8 is a CC chemokine of the monocyte chemoattractant protein (MCP) family whose biological activity and receptor usage have remained elusive. Here we show that CCL8 is highly expressed in the skin, where it serves as an agonist for the chemokine receptor CCR8 but not for CCR2. This distingui...
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| Veröffentlicht in: | Nature immunology 2011-02, Vol.12 (2), p.167-177 |
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| container_title | Nature immunology |
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| creator | Islam, Sabina A Chang, Daniel S Colvin, Richard A Byrne, Mike H McCully, Michelle L Moser, Bernhard Lira, Sergio A Charo, Israel F Luster, Andrew D |
| description | Mouse CCL8 is a CC chemokine of the monocyte chemoattractant protein (MCP) family whose biological activity and receptor usage have remained elusive. Here we show that CCL8 is highly expressed in the skin, where it serves as an agonist for the chemokine receptor CCR8 but not for CCR2. This distinguishes CCL8 from all other MCP chemokines. CCL8 responsiveness defined a population of highly differentiated, CCR8-expressing inflammatory T helper type 2 (T(H)2) cells enriched for interleukin (IL)-5. Ccr8- and Ccl8-deficient mice had markedly less eosinophilic inflammation than wild-type or Ccr4-deficient mice in a model of chronic atopic dermatitis. Adoptive transfer studies established CCR8 as a key regulator of T(H)2 cell recruitment into allergen-inflamed skin. In humans, CCR8 expression also defined an IL-5-enriched T(H)2 cell subset. The CCL8-CCR8 chemokine axis is therefore a crucial regulator of T(H)2 cell homing that drives IL-5-mediated chronic allergic inflammation. |
| doi_str_mv | 10.1038/ni.1984 |
| format | Article |
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Here we show that CCL8 is highly expressed in the skin, where it serves as an agonist for the chemokine receptor CCR8 but not for CCR2. This distinguishes CCL8 from all other MCP chemokines. CCL8 responsiveness defined a population of highly differentiated, CCR8-expressing inflammatory T helper type 2 (T(H)2) cells enriched for interleukin (IL)-5. Ccr8- and Ccl8-deficient mice had markedly less eosinophilic inflammation than wild-type or Ccr4-deficient mice in a model of chronic atopic dermatitis. Adoptive transfer studies established CCR8 as a key regulator of T(H)2 cell recruitment into allergen-inflamed skin. In humans, CCR8 expression also defined an IL-5-enriched T(H)2 cell subset. The CCL8-CCR8 chemokine axis is therefore a crucial regulator of T(H)2 cell homing that drives IL-5-mediated chronic allergic inflammation.</description><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni.1984</identifier><identifier>PMID: 21217759</identifier><language>eng</language><publisher>United States</publisher><subject>Adoptive Transfer ; Animals ; Calcium Signaling - immunology ; Cells, Cultured ; Chemokine CCL1 - genetics ; Chemokine CCL1 - immunology ; Chemokine CCL1 - metabolism ; Chemokine CCL8 - genetics ; Chemokine CCL8 - immunology ; Chemokine CCL8 - metabolism ; Chemotaxis - genetics ; Chemotaxis - immunology ; Cloning, Molecular ; Dermatitis, Atopic - immunology ; Disease Models, Animal ; Humans ; Interleukin-5 - immunology ; Interleukin-5 - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Lymphocyte Homing - immunology ; Skin - pathology ; Th2 Cells - immunology ; Th2 Cells - metabolism ; Th2 Cells - pathology</subject><ispartof>Nature immunology, 2011-02, Vol.12 (2), p.167-177</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21217759$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Islam, Sabina A</creatorcontrib><creatorcontrib>Chang, Daniel S</creatorcontrib><creatorcontrib>Colvin, Richard A</creatorcontrib><creatorcontrib>Byrne, Mike H</creatorcontrib><creatorcontrib>McCully, Michelle L</creatorcontrib><creatorcontrib>Moser, Bernhard</creatorcontrib><creatorcontrib>Lira, Sergio A</creatorcontrib><creatorcontrib>Charo, Israel F</creatorcontrib><creatorcontrib>Luster, Andrew D</creatorcontrib><title>Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ T(H)2 cells</title><title>Nature immunology</title><addtitle>Nat Immunol</addtitle><description>Mouse CCL8 is a CC chemokine of the monocyte chemoattractant protein (MCP) family whose biological activity and receptor usage have remained elusive. 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The CCL8-CCR8 chemokine axis is therefore a crucial regulator of T(H)2 cell homing that drives IL-5-mediated chronic allergic inflammation.</description><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Calcium Signaling - immunology</subject><subject>Cells, Cultured</subject><subject>Chemokine CCL1 - genetics</subject><subject>Chemokine CCL1 - immunology</subject><subject>Chemokine CCL1 - metabolism</subject><subject>Chemokine CCL8 - genetics</subject><subject>Chemokine CCL8 - immunology</subject><subject>Chemokine CCL8 - metabolism</subject><subject>Chemotaxis - genetics</subject><subject>Chemotaxis - immunology</subject><subject>Cloning, Molecular</subject><subject>Dermatitis, Atopic - immunology</subject><subject>Disease Models, Animal</subject><subject>Humans</subject><subject>Interleukin-5 - immunology</subject><subject>Interleukin-5 - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Receptors, Lymphocyte Homing - immunology</subject><subject>Skin - pathology</subject><subject>Th2 Cells - immunology</subject><subject>Th2 Cells - metabolism</subject><subject>Th2 Cells - pathology</subject><issn>1529-2916</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kE1Lw0AYhBdBbK3iP5C9qdjU_c7uUYLaQkSQ6jVsNm_KSvNhdnPovzdiPT0MDMPMIHRFyYoSrh9av6JGixM0p5KZhBmqZug8hC9CqEiVOEMzRhlNU2nm6PO1GwPgLMv1EtuJ7xrbXdf6EJe4H7qmixCwjV3vHa5gaGz00QdcHvAAbhgn0e7wJk_kPd7eru8YdrDfhwt0Wtt9gMsjF-jj-WmbrZP87WWTPeZJTwWJCa0BiJJgBSmZNopqJ6BimmsDtXS2Ai6tkKqSHARwUzsguq6F0qWTSlm-QDd_uVPV7xFCLBoffhvYFqZhhRYyVZIxPjmvj86xbKAq-sE3djgU_1fwH0rCWtE</recordid><startdate>201102</startdate><enddate>201102</enddate><creator>Islam, Sabina A</creator><creator>Chang, Daniel S</creator><creator>Colvin, Richard A</creator><creator>Byrne, Mike H</creator><creator>McCully, Michelle L</creator><creator>Moser, Bernhard</creator><creator>Lira, Sergio A</creator><creator>Charo, Israel F</creator><creator>Luster, Andrew D</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201102</creationdate><title>Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ T(H)2 cells</title><author>Islam, Sabina A ; Chang, Daniel S ; Colvin, Richard A ; Byrne, Mike H ; McCully, Michelle L ; Moser, Bernhard ; Lira, Sergio A ; Charo, Israel F ; Luster, Andrew D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p140t-1fee065ea40b289618c4ed28389ef5cade35a456d53e4e39fce08ff468bc566a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adoptive Transfer</topic><topic>Animals</topic><topic>Calcium Signaling - immunology</topic><topic>Cells, Cultured</topic><topic>Chemokine CCL1 - genetics</topic><topic>Chemokine CCL1 - immunology</topic><topic>Chemokine CCL1 - metabolism</topic><topic>Chemokine CCL8 - genetics</topic><topic>Chemokine CCL8 - immunology</topic><topic>Chemokine CCL8 - metabolism</topic><topic>Chemotaxis - genetics</topic><topic>Chemotaxis - immunology</topic><topic>Cloning, Molecular</topic><topic>Dermatitis, Atopic - immunology</topic><topic>Disease Models, Animal</topic><topic>Humans</topic><topic>Interleukin-5 - immunology</topic><topic>Interleukin-5 - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Receptors, Lymphocyte Homing - immunology</topic><topic>Skin - pathology</topic><topic>Th2 Cells - immunology</topic><topic>Th2 Cells - metabolism</topic><topic>Th2 Cells - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Islam, Sabina A</creatorcontrib><creatorcontrib>Chang, Daniel S</creatorcontrib><creatorcontrib>Colvin, Richard A</creatorcontrib><creatorcontrib>Byrne, Mike H</creatorcontrib><creatorcontrib>McCully, Michelle L</creatorcontrib><creatorcontrib>Moser, Bernhard</creatorcontrib><creatorcontrib>Lira, Sergio A</creatorcontrib><creatorcontrib>Charo, Israel F</creatorcontrib><creatorcontrib>Luster, Andrew D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Islam, Sabina A</au><au>Chang, Daniel S</au><au>Colvin, Richard A</au><au>Byrne, Mike H</au><au>McCully, Michelle L</au><au>Moser, Bernhard</au><au>Lira, Sergio A</au><au>Charo, Israel F</au><au>Luster, Andrew D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ T(H)2 cells</atitle><jtitle>Nature immunology</jtitle><addtitle>Nat Immunol</addtitle><date>2011-02</date><risdate>2011</risdate><volume>12</volume><issue>2</issue><spage>167</spage><epage>177</epage><pages>167-177</pages><eissn>1529-2916</eissn><abstract>Mouse CCL8 is a CC chemokine of the monocyte chemoattractant protein (MCP) family whose biological activity and receptor usage have remained elusive. Here we show that CCL8 is highly expressed in the skin, where it serves as an agonist for the chemokine receptor CCR8 but not for CCR2. This distinguishes CCL8 from all other MCP chemokines. CCL8 responsiveness defined a population of highly differentiated, CCR8-expressing inflammatory T helper type 2 (T(H)2) cells enriched for interleukin (IL)-5. Ccr8- and Ccl8-deficient mice had markedly less eosinophilic inflammation than wild-type or Ccr4-deficient mice in a model of chronic atopic dermatitis. Adoptive transfer studies established CCR8 as a key regulator of T(H)2 cell recruitment into allergen-inflamed skin. In humans, CCR8 expression also defined an IL-5-enriched T(H)2 cell subset. The CCL8-CCR8 chemokine axis is therefore a crucial regulator of T(H)2 cell homing that drives IL-5-mediated chronic allergic inflammation.</abstract><cop>United States</cop><pmid>21217759</pmid><doi>10.1038/ni.1984</doi><tpages>11</tpages></addata></record> |
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| subjects | Adoptive Transfer Animals Calcium Signaling - immunology Cells, Cultured Chemokine CCL1 - genetics Chemokine CCL1 - immunology Chemokine CCL1 - metabolism Chemokine CCL8 - genetics Chemokine CCL8 - immunology Chemokine CCL8 - metabolism Chemotaxis - genetics Chemotaxis - immunology Cloning, Molecular Dermatitis, Atopic - immunology Disease Models, Animal Humans Interleukin-5 - immunology Interleukin-5 - metabolism Mice Mice, Inbred C57BL Mice, Knockout Receptors, Lymphocyte Homing - immunology Skin - pathology Th2 Cells - immunology Th2 Cells - metabolism Th2 Cells - pathology |
| title | Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ T(H)2 cells |
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