The macrophage-TCRαβ is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis
•Identification of a large abundance of TCRαβ+ macrophages within atherosclerotic lesions.•Advanced carotid artery lesions express highly restricted TCRαβ repertoires.•TCR deficient rag−/− mice have an altered macrophage-dependent inflammatory response.•In vitro modulation of macrophage-TCRβ reperto...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2015-01, Vol.456 (1), p.59-65 |
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| creator | Fuchs, Tina Puellmann, Kerstin Emmert, Alexander Fleig, Julian Oniga, Septimia Laird, Rebecca Heida, Nana Maria Schäfer, Katrin Neumaier, Michael Beham, Alexander W. Kaminski, Wolfgang E. |
| description | •Identification of a large abundance of TCRαβ+ macrophages within atherosclerotic lesions.•Advanced carotid artery lesions express highly restricted TCRαβ repertoires.•TCR deficient rag−/− mice have an altered macrophage-dependent inflammatory response.•In vitro modulation of macrophage-TCRβ repertoires by cholesterol.
Recent evidence indicates constitutive expression of a recombinatorial TCRαβ immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCRβ repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCRαβ+ macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag−/− mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCRαβ bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCRαβ repertoires that are characterized by a striking usage of the Vβ22 and Vβ16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCRαβ signatures. Our results implicate the macrophage-TCRαβ combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease. |
| doi_str_mv | 10.1016/j.bbrc.2014.11.034 |
| format | Article |
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Recent evidence indicates constitutive expression of a recombinatorial TCRαβ immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCRβ repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCRαβ+ macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag−/− mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCRαβ bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCRαβ repertoires that are characterized by a striking usage of the Vβ22 and Vβ16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCRαβ signatures. Our results implicate the macrophage-TCRαβ combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2014.11.034</identifier><identifier>PMID: 25446098</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Atherosclerosis ; Atherosclerosis - genetics ; Atherosclerosis - immunology ; Atherosclerosis - metabolism ; Carotid Arteries - pathology ; Carotid Artery Diseases - metabolism ; Cholesterol - metabolism ; Cholesterol, LDL - metabolism ; Complementarity Determining Regions - metabolism ; Endarterectomy, Carotid ; Female ; Homeodomain Proteins - genetics ; Humans ; Inflammation ; Lipopolysaccharide Receptors - metabolism ; Macrophage ; Macrophages - cytology ; Macrophages - immunology ; Macrophages - metabolism ; Male ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Receptors, Antigen, T-Cell, alpha-beta - immunology ; Sequence Homology, Amino Acid ; TCR ; V(D)J immune receptor ; V(D)J Recombination</subject><ispartof>Biochemical and biophysical research communications, 2015-01, Vol.456 (1), p.59-65</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c271t-e40e859ed3ef19416d8eaa2f976799540302069da65ee839276c49b2387476ae3</citedby><cites>FETCH-LOGICAL-c271t-e40e859ed3ef19416d8eaa2f976799540302069da65ee839276c49b2387476ae3</cites><orcidid>0000-0003-0410-3931</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2014.11.034$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25446098$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fuchs, Tina</creatorcontrib><creatorcontrib>Puellmann, Kerstin</creatorcontrib><creatorcontrib>Emmert, Alexander</creatorcontrib><creatorcontrib>Fleig, Julian</creatorcontrib><creatorcontrib>Oniga, Septimia</creatorcontrib><creatorcontrib>Laird, Rebecca</creatorcontrib><creatorcontrib>Heida, Nana Maria</creatorcontrib><creatorcontrib>Schäfer, Katrin</creatorcontrib><creatorcontrib>Neumaier, Michael</creatorcontrib><creatorcontrib>Beham, Alexander W.</creatorcontrib><creatorcontrib>Kaminski, Wolfgang E.</creatorcontrib><title>The macrophage-TCRαβ is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>•Identification of a large abundance of TCRαβ+ macrophages within atherosclerotic lesions.•Advanced carotid artery lesions express highly restricted TCRαβ repertoires.•TCR deficient rag−/− mice have an altered macrophage-dependent inflammatory response.•In vitro modulation of macrophage-TCRβ repertoires by cholesterol.
Recent evidence indicates constitutive expression of a recombinatorial TCRαβ immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCRβ repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCRαβ+ macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag−/− mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCRαβ bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCRαβ repertoires that are characterized by a striking usage of the Vβ22 and Vβ16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCRαβ signatures. Our results implicate the macrophage-TCRαβ combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - genetics</subject><subject>Atherosclerosis - immunology</subject><subject>Atherosclerosis - metabolism</subject><subject>Carotid Arteries - pathology</subject><subject>Carotid Artery Diseases - metabolism</subject><subject>Cholesterol - metabolism</subject><subject>Cholesterol, LDL - metabolism</subject><subject>Complementarity Determining Regions - metabolism</subject><subject>Endarterectomy, Carotid</subject><subject>Female</subject><subject>Homeodomain Proteins - genetics</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Lipopolysaccharide Receptors - metabolism</subject><subject>Macrophage</subject><subject>Macrophages - cytology</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - immunology</subject><subject>Sequence Homology, Amino Acid</subject><subject>TCR</subject><subject>V(D)J immune receptor</subject><subject>V(D)J Recombination</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFq3DAQhkVoSLZpXqCHomMvdmdkrWxBLmFJ2kKgEDbQm5Dl2awW23Ilb6CP1TxInilaNu2xl5nh558f_o-xjwglAqovu7JtoysFoCwRS6jkCVsgaCgEgnzHFgCgCqHx5zl7n9IOAFEqfcbOxVJKBbpZsLjeEh-si2Ha2kcq1qv7lz8vz9wnbrnbhp7STDH0RaQ0hTH5J-IuDK0f7Ryitz33w7AfiUdyNGWJ27HL2tR7Z2fK58jtvM0RyfWH6dMHdrqxfaLLt33BHm5v1qtvxd2Pr99X13eFEzXOBUmgZqmpq2iDWqLqGrJWbHStaq2XEioQoHRn1ZKoqbSolZO6FVVTy1pZqi7Y52PuFMOvfe5hBp8c9b0dKeyTQSVBNkJila3iaM0cUoq0MVP0g42_DYI5sDY7c2BtDqwNosms89Ont_x9O1D37-Uv3Gy4Ohoot3zyFE1ynkZHnc-0ZtMF_7_8V4xkkrs</recordid><startdate>20150102</startdate><enddate>20150102</enddate><creator>Fuchs, Tina</creator><creator>Puellmann, Kerstin</creator><creator>Emmert, Alexander</creator><creator>Fleig, Julian</creator><creator>Oniga, Septimia</creator><creator>Laird, Rebecca</creator><creator>Heida, Nana Maria</creator><creator>Schäfer, Katrin</creator><creator>Neumaier, Michael</creator><creator>Beham, Alexander W.</creator><creator>Kaminski, Wolfgang E.</creator><general>Elsevier Inc</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><orcidid>https://orcid.org/0000-0003-0410-3931</orcidid></search><sort><creationdate>20150102</creationdate><title>The macrophage-TCRαβ is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis</title><author>Fuchs, Tina ; Puellmann, Kerstin ; Emmert, Alexander ; Fleig, Julian ; Oniga, Septimia ; Laird, Rebecca ; Heida, Nana Maria ; Schäfer, Katrin ; Neumaier, Michael ; Beham, Alexander W. ; Kaminski, Wolfgang E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c271t-e40e859ed3ef19416d8eaa2f976799540302069da65ee839276c49b2387476ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis - genetics</topic><topic>Atherosclerosis - immunology</topic><topic>Atherosclerosis - metabolism</topic><topic>Carotid Arteries - pathology</topic><topic>Carotid Artery Diseases - metabolism</topic><topic>Cholesterol - metabolism</topic><topic>Cholesterol, LDL - metabolism</topic><topic>Complementarity Determining Regions - metabolism</topic><topic>Endarterectomy, Carotid</topic><topic>Female</topic><topic>Homeodomain Proteins - genetics</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Lipopolysaccharide Receptors - metabolism</topic><topic>Macrophage</topic><topic>Macrophages - cytology</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Molecular Sequence Data</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - immunology</topic><topic>Sequence Homology, Amino Acid</topic><topic>TCR</topic><topic>V(D)J immune receptor</topic><topic>V(D)J Recombination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fuchs, Tina</creatorcontrib><creatorcontrib>Puellmann, Kerstin</creatorcontrib><creatorcontrib>Emmert, Alexander</creatorcontrib><creatorcontrib>Fleig, Julian</creatorcontrib><creatorcontrib>Oniga, Septimia</creatorcontrib><creatorcontrib>Laird, Rebecca</creatorcontrib><creatorcontrib>Heida, Nana Maria</creatorcontrib><creatorcontrib>Schäfer, Katrin</creatorcontrib><creatorcontrib>Neumaier, Michael</creatorcontrib><creatorcontrib>Beham, Alexander W.</creatorcontrib><creatorcontrib>Kaminski, Wolfgang E.</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><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fuchs, Tina</au><au>Puellmann, Kerstin</au><au>Emmert, Alexander</au><au>Fleig, Julian</au><au>Oniga, Septimia</au><au>Laird, Rebecca</au><au>Heida, Nana Maria</au><au>Schäfer, Katrin</au><au>Neumaier, Michael</au><au>Beham, Alexander W.</au><au>Kaminski, Wolfgang E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The macrophage-TCRαβ is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2015-01-02</date><risdate>2015</risdate><volume>456</volume><issue>1</issue><spage>59</spage><epage>65</epage><pages>59-65</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>•Identification of a large abundance of TCRαβ+ macrophages within atherosclerotic lesions.•Advanced carotid artery lesions express highly restricted TCRαβ repertoires.•TCR deficient rag−/− mice have an altered macrophage-dependent inflammatory response.•In vitro modulation of macrophage-TCRβ repertoires by cholesterol.
Recent evidence indicates constitutive expression of a recombinatorial TCRαβ immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCRβ repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCRαβ+ macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag−/− mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCRαβ bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCRαβ repertoires that are characterized by a striking usage of the Vβ22 and Vβ16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCRαβ signatures. Our results implicate the macrophage-TCRαβ combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25446098</pmid><doi>10.1016/j.bbrc.2014.11.034</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-0410-3931</orcidid></addata></record> |
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| subjects | Amino Acid Sequence Animals Atherosclerosis Atherosclerosis - genetics Atherosclerosis - immunology Atherosclerosis - metabolism Carotid Arteries - pathology Carotid Artery Diseases - metabolism Cholesterol - metabolism Cholesterol, LDL - metabolism Complementarity Determining Regions - metabolism Endarterectomy, Carotid Female Homeodomain Proteins - genetics Humans Inflammation Lipopolysaccharide Receptors - metabolism Macrophage Macrophages - cytology Macrophages - immunology Macrophages - metabolism Male Mice Mice, Transgenic Molecular Sequence Data Receptors, Antigen, T-Cell, alpha-beta - immunology Sequence Homology, Amino Acid TCR V(D)J immune receptor V(D)J Recombination |
| title | The macrophage-TCRαβ is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis |
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