Autoantigens act as tissue-specific chemoattractants
We have investigated the chemoattractant properties of self‐antigens associated with autoimmune diseases and solid tumors. Many autoantigens induced leukocyte migration, especially by immature dendritic cells (iDC) by interacting with various chemoattractant Gi‐protein‐coupled receptors (GiPCR). Our...
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description | We have investigated the chemoattractant properties of self‐antigens associated with autoimmune diseases and solid tumors. Many autoantigens induced leukocyte migration, especially by immature dendritic cells (iDC) by interacting with various chemoattractant Gi‐protein‐coupled receptors (GiPCR). Our initial observation that myositis‐associated autoantigens, histidyl‐tRNA synthetase and asparaginyl‐tRNA synthetase, were chemotactic for CC chemokine receptor 5 (CCR5)‐ and CCR3‐expressing leukocytes, while other nonautoantigenic aminoacyl‐tRNA synthesases were not, suggested that only self‐antigens capable of interacting with receptors on antigen‐presenting cells were immunogenic. We next determined that self‐antigens associated with autoimmune diseases, e.g., multiple sclerosis or experimental autoimmune encephalomyelitis, type I diabetes, scleroderma, systemic lupus erythematosus, autoimmune uveitis, or experimental autoimmune uveitis (EAU), were chemotactic for GiPCR expressed by iDC. The majority of autoantigens were DC chemoattractants at 10–100 ng/ml, but did not induce DC maturation until they reached 1000‐fold higher concentrations. Interphotoreceptor retinoid‐binding protein and retinal arrestin (S‐antigen) are targets of autoantibodies in human uveitis and are chemotactic for CXC chemokine receptor 5 (CXCR5)‐ and/or CXCR3‐expressing iDC. However, although S‐antigen does not induce EAU in wild‐type mice, it is nevertheless a chemoattractant for murine iDC. These unexpected observations suggested that the chemotactic activity of these tissue‐specific self‐antigens could be involved in promotion of tissue repair and restoration. Thus, the primary role of autoantigens may be to alert the immune system to danger signals from invaded and damaged tissues to facilitate repair, and autoimmune responses subsequently develop only in subjects with impaired immunoregulatory function. |
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M. Zack</creator><creatorcontrib>Oppenheim, Joost J. ; Dong, Hui Fang ; Plotz, Paul ; Caspi, Rachel R. ; Dykstra, Michelle ; Pierce, Susan ; Martin, Roland ; Carlos, Casey ; Finn, Olivera ; Koul, Omanand ; Howard, O. M. Zack</creatorcontrib><description>We have investigated the chemoattractant properties of self‐antigens associated with autoimmune diseases and solid tumors. Many autoantigens induced leukocyte migration, especially by immature dendritic cells (iDC) by interacting with various chemoattractant Gi‐protein‐coupled receptors (GiPCR). Our initial observation that myositis‐associated autoantigens, histidyl‐tRNA synthetase and asparaginyl‐tRNA synthetase, were chemotactic for CC chemokine receptor 5 (CCR5)‐ and CCR3‐expressing leukocytes, while other nonautoantigenic aminoacyl‐tRNA synthesases were not, suggested that only self‐antigens capable of interacting with receptors on antigen‐presenting cells were immunogenic. We next determined that self‐antigens associated with autoimmune diseases, e.g., multiple sclerosis or experimental autoimmune encephalomyelitis, type I diabetes, scleroderma, systemic lupus erythematosus, autoimmune uveitis, or experimental autoimmune uveitis (EAU), were chemotactic for GiPCR expressed by iDC. The majority of autoantigens were DC chemoattractants at 10–100 ng/ml, but did not induce DC maturation until they reached 1000‐fold higher concentrations. Interphotoreceptor retinoid‐binding protein and retinal arrestin (S‐antigen) are targets of autoantibodies in human uveitis and are chemotactic for CXC chemokine receptor 5 (CXCR5)‐ and/or CXCR3‐expressing iDC. However, although S‐antigen does not induce EAU in wild‐type mice, it is nevertheless a chemoattractant for murine iDC. These unexpected observations suggested that the chemotactic activity of these tissue‐specific self‐antigens could be involved in promotion of tissue repair and restoration. Thus, the primary role of autoantigens may be to alert the immune system to danger signals from invaded and damaged tissues to facilitate repair, and autoimmune responses subsequently develop only in subjects with impaired immunoregulatory function.</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.1004623</identifier><identifier>PMID: 15917448</identifier><language>eng</language><publisher>United States: Society for Leukocyte Biology</publisher><subject>Animals ; Antigens, Neoplasm - immunology ; Autoantigens - immunology ; Autoimmune Diseases - immunology ; chemokines ; Chemotactic Factors - immunology ; chemotaxis ; Chemotaxis, Leukocyte - immunology ; dendritic cells ; Dendritic Cells - immunology ; Humans ; Leukocytes, Mononuclear - immunology ; Mice ; migrations ; Neoplasms - immunology ; tumor antigens</subject><ispartof>Journal of leukocyte biology, 2005-06, Vol.77 (6), p.854-861</ispartof><rights>2005 Society for Leukocyte Biology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4924-cbe9e8ea8afdc886d7440e9bf90629ccf3dd77b6a406b867c0894ada011ae8b33</citedby><cites>FETCH-LOGICAL-c4924-cbe9e8ea8afdc886d7440e9bf90629ccf3dd77b6a406b867c0894ada011ae8b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.1004623$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.1004623$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15917448$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oppenheim, Joost J.</creatorcontrib><creatorcontrib>Dong, Hui Fang</creatorcontrib><creatorcontrib>Plotz, Paul</creatorcontrib><creatorcontrib>Caspi, Rachel R.</creatorcontrib><creatorcontrib>Dykstra, Michelle</creatorcontrib><creatorcontrib>Pierce, Susan</creatorcontrib><creatorcontrib>Martin, Roland</creatorcontrib><creatorcontrib>Carlos, Casey</creatorcontrib><creatorcontrib>Finn, Olivera</creatorcontrib><creatorcontrib>Koul, Omanand</creatorcontrib><creatorcontrib>Howard, O. M. Zack</creatorcontrib><title>Autoantigens act as tissue-specific chemoattractants</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><description>We have investigated the chemoattractant properties of self‐antigens associated with autoimmune diseases and solid tumors. Many autoantigens induced leukocyte migration, especially by immature dendritic cells (iDC) by interacting with various chemoattractant Gi‐protein‐coupled receptors (GiPCR). Our initial observation that myositis‐associated autoantigens, histidyl‐tRNA synthetase and asparaginyl‐tRNA synthetase, were chemotactic for CC chemokine receptor 5 (CCR5)‐ and CCR3‐expressing leukocytes, while other nonautoantigenic aminoacyl‐tRNA synthesases were not, suggested that only self‐antigens capable of interacting with receptors on antigen‐presenting cells were immunogenic. We next determined that self‐antigens associated with autoimmune diseases, e.g., multiple sclerosis or experimental autoimmune encephalomyelitis, type I diabetes, scleroderma, systemic lupus erythematosus, autoimmune uveitis, or experimental autoimmune uveitis (EAU), were chemotactic for GiPCR expressed by iDC. The majority of autoantigens were DC chemoattractants at 10–100 ng/ml, but did not induce DC maturation until they reached 1000‐fold higher concentrations. Interphotoreceptor retinoid‐binding protein and retinal arrestin (S‐antigen) are targets of autoantibodies in human uveitis and are chemotactic for CXC chemokine receptor 5 (CXCR5)‐ and/or CXCR3‐expressing iDC. However, although S‐antigen does not induce EAU in wild‐type mice, it is nevertheless a chemoattractant for murine iDC. These unexpected observations suggested that the chemotactic activity of these tissue‐specific self‐antigens could be involved in promotion of tissue repair and restoration. Thus, the primary role of autoantigens may be to alert the immune system to danger signals from invaded and damaged tissues to facilitate repair, and autoimmune responses subsequently develop only in subjects with impaired immunoregulatory function.</description><subject>Animals</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Autoantigens - immunology</subject><subject>Autoimmune Diseases - immunology</subject><subject>chemokines</subject><subject>Chemotactic Factors - immunology</subject><subject>chemotaxis</subject><subject>Chemotaxis, Leukocyte - immunology</subject><subject>dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Humans</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Mice</subject><subject>migrations</subject><subject>Neoplasms - immunology</subject><subject>tumor antigens</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0D1PwzAQBmALgWgpTOyoCywo5Ry7_hhLxacqscBsOc6ldZU0JU4U9d_jqpXYYPJwz70nv4RcU5hQqvTDuswmFICLlJ2QIdVMJUxIdkqGIDlNphxgQC5CWAMASwWckwGdaio5V0PCZ11b203rl7gJY-vasQ3j1ofQYRK26Hzh3ditsKpt2zZxHm24JGeFLQNeHd8R-Xp--py_JouPl7f5bJE4rlOeuAw1KrTKFrlTSuTxJKDOCg0i1c4VLM-lzITlIDIlpAOluc0tUGpRZYyNyN0hd9vU3x2G1lQ-OCxLu8G6C0ZIJdlU6n9h_KzmqdjD-wN0TR1Cg4XZNr6yzc5QMPs2TWzTHNuM-uYY22UV5r_2WF8EcAC9L3H3V5Z5XzyCmvK4cntYWfnlqvcNmlDZsowXUtP3vZRGmL37AYdfjBY</recordid><startdate>20050601</startdate><enddate>20050601</enddate><creator>Oppenheim, Joost J.</creator><creator>Dong, Hui Fang</creator><creator>Plotz, Paul</creator><creator>Caspi, Rachel R.</creator><creator>Dykstra, Michelle</creator><creator>Pierce, Susan</creator><creator>Martin, Roland</creator><creator>Carlos, Casey</creator><creator>Finn, Olivera</creator><creator>Koul, Omanand</creator><creator>Howard, O. 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Zack</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4924-cbe9e8ea8afdc886d7440e9bf90629ccf3dd77b6a406b867c0894ada011ae8b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Autoantigens - immunology</topic><topic>Autoimmune Diseases - immunology</topic><topic>chemokines</topic><topic>Chemotactic Factors - immunology</topic><topic>chemotaxis</topic><topic>Chemotaxis, Leukocyte - immunology</topic><topic>dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Humans</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Mice</topic><topic>migrations</topic><topic>Neoplasms - immunology</topic><topic>tumor antigens</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oppenheim, Joost J.</creatorcontrib><creatorcontrib>Dong, Hui Fang</creatorcontrib><creatorcontrib>Plotz, Paul</creatorcontrib><creatorcontrib>Caspi, Rachel R.</creatorcontrib><creatorcontrib>Dykstra, Michelle</creatorcontrib><creatorcontrib>Pierce, Susan</creatorcontrib><creatorcontrib>Martin, Roland</creatorcontrib><creatorcontrib>Carlos, Casey</creatorcontrib><creatorcontrib>Finn, Olivera</creatorcontrib><creatorcontrib>Koul, Omanand</creatorcontrib><creatorcontrib>Howard, O. 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Zack</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autoantigens act as tissue-specific chemoattractants</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>77</volume><issue>6</issue><spage>854</spage><epage>861</epage><pages>854-861</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>We have investigated the chemoattractant properties of self‐antigens associated with autoimmune diseases and solid tumors. Many autoantigens induced leukocyte migration, especially by immature dendritic cells (iDC) by interacting with various chemoattractant Gi‐protein‐coupled receptors (GiPCR). Our initial observation that myositis‐associated autoantigens, histidyl‐tRNA synthetase and asparaginyl‐tRNA synthetase, were chemotactic for CC chemokine receptor 5 (CCR5)‐ and CCR3‐expressing leukocytes, while other nonautoantigenic aminoacyl‐tRNA synthesases were not, suggested that only self‐antigens capable of interacting with receptors on antigen‐presenting cells were immunogenic. We next determined that self‐antigens associated with autoimmune diseases, e.g., multiple sclerosis or experimental autoimmune encephalomyelitis, type I diabetes, scleroderma, systemic lupus erythematosus, autoimmune uveitis, or experimental autoimmune uveitis (EAU), were chemotactic for GiPCR expressed by iDC. The majority of autoantigens were DC chemoattractants at 10–100 ng/ml, but did not induce DC maturation until they reached 1000‐fold higher concentrations. Interphotoreceptor retinoid‐binding protein and retinal arrestin (S‐antigen) are targets of autoantibodies in human uveitis and are chemotactic for CXC chemokine receptor 5 (CXCR5)‐ and/or CXCR3‐expressing iDC. However, although S‐antigen does not induce EAU in wild‐type mice, it is nevertheless a chemoattractant for murine iDC. These unexpected observations suggested that the chemotactic activity of these tissue‐specific self‐antigens could be involved in promotion of tissue repair and restoration. Thus, the primary role of autoantigens may be to alert the immune system to danger signals from invaded and damaged tissues to facilitate repair, and autoimmune responses subsequently develop only in subjects with impaired immunoregulatory function.</abstract><cop>United States</cop><pub>Society for Leukocyte Biology</pub><pmid>15917448</pmid><doi>10.1189/jlb.1004623</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antigens, Neoplasm - immunology Autoantigens - immunology Autoimmune Diseases - immunology chemokines Chemotactic Factors - immunology chemotaxis Chemotaxis, Leukocyte - immunology dendritic cells Dendritic Cells - immunology Humans Leukocytes, Mononuclear - immunology Mice migrations Neoplasms - immunology tumor antigens |
title | Autoantigens act as tissue-specific chemoattractants |
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