RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo
The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which we...
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| Veröffentlicht in: | Molecular therapy 2018-01, Vol.26 (1), p.95-104 |
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| creator | Fülle, Lorenz Steiner, Nancy Funke, Markus Gondorf, Fabian Pfeiffer, Franziska Siegl, Julia Opitz, Friederike V. Haßel, Silvana K. Erazo, Anna Belen Schanz, Oliver Stunden, H. James Blank, Michael Gröber, Carsten Händler, Kristian Beyer, Marc Weighardt, Heike Latz, Eicke Schultze, Joachim L. Mayer, Günter Förster, Irmgard |
| description | The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17. Both aptamers efficiently inhibited the directed migration of the CCR4+ lymphoma line BW5147.3 toward CCL17 in a dose-dependent manner. To study the effect of these aptamers in vivo, we used a murine model of contact hypersensitivity. Systemic application of the aptamers significantly prevented ear swelling and T cell infiltration into the ears of sensitized mice after challenge with the contact sensitizer. The results of this proof-of-principle study establish aptamers as potent inhibitors of CCL17-mediated chemotaxis. Potentially, CCL17-specific aptamers may be used therapeutically in humans to treat or prevent allergic and inflammatory diseases.
[Display omitted]
The chemokine CCL17 promotes T cell attraction to peripheral tissues and thereby exacerbates inflammatory reactions. Using SELEX, Fülle et al. selected high-affinity aptamers, which neutralize CCL17 in murine contact hypersensitivity. Because of their small size and structural properties, such aptamers may represent new versatile drugs for allergic skin diseases. |
| doi_str_mv | 10.1016/j.ymthe.2017.10.005 |
| format | Article |
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[Display omitted]
The chemokine CCL17 promotes T cell attraction to peripheral tissues and thereby exacerbates inflammatory reactions. Using SELEX, Fülle et al. selected high-affinity aptamers, which neutralize CCL17 in murine contact hypersensitivity. Because of their small size and structural properties, such aptamers may represent new versatile drugs for allergic skin diseases.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1016/j.ymthe.2017.10.005</identifier><identifier>PMID: 29103909</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Abdomen ; allergy ; Animal models ; Animals ; aptamer ; Aptamers ; Aptamers, Nucleotide - chemistry ; Aptamers, Nucleotide - genetics ; Biomarkers ; CCL17 ; CCL17 protein ; CCL22 ; Cell adhesion & migration ; cell migration ; Cell Movement - genetics ; chemokine ; Chemokine CCL17 - genetics ; Chemokines ; Chemotaxis ; Chemotaxis - genetics ; Chemotaxis - immunology ; Contact dermatitis ; contact hypersensitivity ; Dendritic cells ; Dermatitis ; Dermatitis, Contact - genetics ; Dermatitis, Contact - immunology ; Disease Models, Animal ; Ear ; Experiments ; Female ; Gene Expression Regulation ; Humans ; Hypersensitivity ; Immune system ; Inflammatory diseases ; Leukocyte migration ; Ligands ; Lymphocytes T ; Lymphoma ; Macrophages - immunology ; Macrophages - metabolism ; Mice ; Nucleic Acid Conformation ; Olive oil ; Original ; Retention ; Ribonucleic acid ; RNA ; SELEX ; SELEX Aptamer Technique ; skin homing ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; TARC</subject><ispartof>Molecular therapy, 2018-01, Vol.26 (1), p.95-104</ispartof><rights>2017 The Author(s)</rights><rights>Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><rights>2017. The Author(s)</rights><rights>2017 The Author(s) 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4025-cdf2be054f117fa923ca261a871361f097329b96327d5d35b44885c319d180423</citedby><cites>FETCH-LOGICAL-c4025-cdf2be054f117fa923ca261a871361f097329b96327d5d35b44885c319d180423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763148/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763148/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29103909$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fülle, Lorenz</creatorcontrib><creatorcontrib>Steiner, Nancy</creatorcontrib><creatorcontrib>Funke, Markus</creatorcontrib><creatorcontrib>Gondorf, Fabian</creatorcontrib><creatorcontrib>Pfeiffer, Franziska</creatorcontrib><creatorcontrib>Siegl, Julia</creatorcontrib><creatorcontrib>Opitz, Friederike V.</creatorcontrib><creatorcontrib>Haßel, Silvana K.</creatorcontrib><creatorcontrib>Erazo, Anna Belen</creatorcontrib><creatorcontrib>Schanz, Oliver</creatorcontrib><creatorcontrib>Stunden, H. James</creatorcontrib><creatorcontrib>Blank, Michael</creatorcontrib><creatorcontrib>Gröber, Carsten</creatorcontrib><creatorcontrib>Händler, Kristian</creatorcontrib><creatorcontrib>Beyer, Marc</creatorcontrib><creatorcontrib>Weighardt, Heike</creatorcontrib><creatorcontrib>Latz, Eicke</creatorcontrib><creatorcontrib>Schultze, Joachim L.</creatorcontrib><creatorcontrib>Mayer, Günter</creatorcontrib><creatorcontrib>Förster, Irmgard</creatorcontrib><title>RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17. Both aptamers efficiently inhibited the directed migration of the CCR4+ lymphoma line BW5147.3 toward CCL17 in a dose-dependent manner. To study the effect of these aptamers in vivo, we used a murine model of contact hypersensitivity. Systemic application of the aptamers significantly prevented ear swelling and T cell infiltration into the ears of sensitized mice after challenge with the contact sensitizer. The results of this proof-of-principle study establish aptamers as potent inhibitors of CCL17-mediated chemotaxis. Potentially, CCL17-specific aptamers may be used therapeutically in humans to treat or prevent allergic and inflammatory diseases.
[Display omitted]
The chemokine CCL17 promotes T cell attraction to peripheral tissues and thereby exacerbates inflammatory reactions. Using SELEX, Fülle et al. selected high-affinity aptamers, which neutralize CCL17 in murine contact hypersensitivity. Because of their small size and structural properties, such aptamers may represent new versatile drugs for allergic skin diseases.</description><subject>Abdomen</subject><subject>allergy</subject><subject>Animal models</subject><subject>Animals</subject><subject>aptamer</subject><subject>Aptamers</subject><subject>Aptamers, Nucleotide - chemistry</subject><subject>Aptamers, Nucleotide - genetics</subject><subject>Biomarkers</subject><subject>CCL17</subject><subject>CCL17 protein</subject><subject>CCL22</subject><subject>Cell adhesion & migration</subject><subject>cell migration</subject><subject>Cell Movement - genetics</subject><subject>chemokine</subject><subject>Chemokine CCL17 - genetics</subject><subject>Chemokines</subject><subject>Chemotaxis</subject><subject>Chemotaxis - genetics</subject><subject>Chemotaxis - immunology</subject><subject>Contact dermatitis</subject><subject>contact hypersensitivity</subject><subject>Dendritic cells</subject><subject>Dermatitis</subject><subject>Dermatitis, Contact - genetics</subject><subject>Dermatitis, Contact - immunology</subject><subject>Disease Models, Animal</subject><subject>Ear</subject><subject>Experiments</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Hypersensitivity</subject><subject>Immune system</subject><subject>Inflammatory diseases</subject><subject>Leukocyte migration</subject><subject>Ligands</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Nucleic Acid Conformation</subject><subject>Olive oil</subject><subject>Original</subject><subject>Retention</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>SELEX</subject><subject>SELEX Aptamer Technique</subject><subject>skin homing</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><subject>TARC</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcGO0zAQjRCIXRa-AAlZ4rKXFo8dO_EBpCoCdqUC0mrhajmO07pK7GI7FeVr-Ba-DHe7VMCBk0fj997Mm1cUzwHPAQN_tZnvx7Q2c4Khyp05xuxBcQ6MsBnGpHx4qoGfFU9i3OQKmOCPizMiAFOBxXkx3HxcoMU2qdGEiG6M9itnv1u3Qh-mYJ1BTbOECl27tW1tQreoMcOAmrUZfVLfbETKdZnWTTpDvUtKJ3S132Yx46JNdmfTPrN__vhid_5p8ahXQzTP7t-L4vO7t7fN1Wz56f11s1jOdInzxrrrSWswK3uAqleCUK0IB1VXQDn0WFSUiFZwSqqOdZS1ZVnXTFMQHdS4JPSieHPU3U7taDptXApqkNtgRxX20isr__5xdi1XfidZxSmUdRa4vBcI_utkYpKjjTo7V874KUoQPB-QYzjMevkPdOOn4LI9SUDUGFccs4yiR5QOPsZg-tMygOUhTbmRd2nKQ5qHJr5jvfjTx4nzO74MeH0EmHzNnTVBRm2N06azwegkO2__O-AX6XaxMg</recordid><startdate>20180103</startdate><enddate>20180103</enddate><creator>Fülle, Lorenz</creator><creator>Steiner, Nancy</creator><creator>Funke, Markus</creator><creator>Gondorf, Fabian</creator><creator>Pfeiffer, Franziska</creator><creator>Siegl, Julia</creator><creator>Opitz, Friederike V.</creator><creator>Haßel, Silvana K.</creator><creator>Erazo, Anna Belen</creator><creator>Schanz, Oliver</creator><creator>Stunden, H. 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James ; Blank, Michael ; Gröber, Carsten ; Händler, Kristian ; Beyer, Marc ; Weighardt, Heike ; Latz, Eicke ; Schultze, Joachim L. ; Mayer, Günter ; Förster, Irmgard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4025-cdf2be054f117fa923ca261a871361f097329b96327d5d35b44885c319d180423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Abdomen</topic><topic>allergy</topic><topic>Animal models</topic><topic>Animals</topic><topic>aptamer</topic><topic>Aptamers</topic><topic>Aptamers, Nucleotide - chemistry</topic><topic>Aptamers, Nucleotide - genetics</topic><topic>Biomarkers</topic><topic>CCL17</topic><topic>CCL17 protein</topic><topic>CCL22</topic><topic>Cell adhesion & migration</topic><topic>cell migration</topic><topic>Cell Movement - genetics</topic><topic>chemokine</topic><topic>Chemokine CCL17 - genetics</topic><topic>Chemokines</topic><topic>Chemotaxis</topic><topic>Chemotaxis - genetics</topic><topic>Chemotaxis - immunology</topic><topic>Contact dermatitis</topic><topic>contact hypersensitivity</topic><topic>Dendritic cells</topic><topic>Dermatitis</topic><topic>Dermatitis, Contact - genetics</topic><topic>Dermatitis, Contact - immunology</topic><topic>Disease Models, Animal</topic><topic>Ear</topic><topic>Experiments</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Hypersensitivity</topic><topic>Immune system</topic><topic>Inflammatory diseases</topic><topic>Leukocyte migration</topic><topic>Ligands</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Nucleic Acid Conformation</topic><topic>Olive oil</topic><topic>Original</topic><topic>Retention</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>SELEX</topic><topic>SELEX Aptamer Technique</topic><topic>skin homing</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><topic>TARC</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fülle, Lorenz</creatorcontrib><creatorcontrib>Steiner, Nancy</creatorcontrib><creatorcontrib>Funke, Markus</creatorcontrib><creatorcontrib>Gondorf, Fabian</creatorcontrib><creatorcontrib>Pfeiffer, Franziska</creatorcontrib><creatorcontrib>Siegl, Julia</creatorcontrib><creatorcontrib>Opitz, Friederike V.</creatorcontrib><creatorcontrib>Haßel, Silvana K.</creatorcontrib><creatorcontrib>Erazo, Anna Belen</creatorcontrib><creatorcontrib>Schanz, Oliver</creatorcontrib><creatorcontrib>Stunden, H. 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James</au><au>Blank, Michael</au><au>Gröber, Carsten</au><au>Händler, Kristian</au><au>Beyer, Marc</au><au>Weighardt, Heike</au><au>Latz, Eicke</au><au>Schultze, Joachim L.</au><au>Mayer, Günter</au><au>Förster, Irmgard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo</atitle><jtitle>Molecular therapy</jtitle><addtitle>Mol Ther</addtitle><date>2018-01-03</date><risdate>2018</risdate><volume>26</volume><issue>1</issue><spage>95</spage><epage>104</epage><pages>95-104</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17. Both aptamers efficiently inhibited the directed migration of the CCR4+ lymphoma line BW5147.3 toward CCL17 in a dose-dependent manner. To study the effect of these aptamers in vivo, we used a murine model of contact hypersensitivity. Systemic application of the aptamers significantly prevented ear swelling and T cell infiltration into the ears of sensitized mice after challenge with the contact sensitizer. The results of this proof-of-principle study establish aptamers as potent inhibitors of CCL17-mediated chemotaxis. Potentially, CCL17-specific aptamers may be used therapeutically in humans to treat or prevent allergic and inflammatory diseases.
[Display omitted]
The chemokine CCL17 promotes T cell attraction to peripheral tissues and thereby exacerbates inflammatory reactions. Using SELEX, Fülle et al. selected high-affinity aptamers, which neutralize CCL17 in murine contact hypersensitivity. Because of their small size and structural properties, such aptamers may represent new versatile drugs for allergic skin diseases.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29103909</pmid><doi>10.1016/j.ymthe.2017.10.005</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular therapy, 2018-01, Vol.26 (1), p.95-104 |
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| subjects | Abdomen allergy Animal models Animals aptamer Aptamers Aptamers, Nucleotide - chemistry Aptamers, Nucleotide - genetics Biomarkers CCL17 CCL17 protein CCL22 Cell adhesion & migration cell migration Cell Movement - genetics chemokine Chemokine CCL17 - genetics Chemokines Chemotaxis Chemotaxis - genetics Chemotaxis - immunology Contact dermatitis contact hypersensitivity Dendritic cells Dermatitis Dermatitis, Contact - genetics Dermatitis, Contact - immunology Disease Models, Animal Ear Experiments Female Gene Expression Regulation Humans Hypersensitivity Immune system Inflammatory diseases Leukocyte migration Ligands Lymphocytes T Lymphoma Macrophages - immunology Macrophages - metabolism Mice Nucleic Acid Conformation Olive oil Original Retention Ribonucleic acid RNA SELEX SELEX Aptamer Technique skin homing T-Lymphocytes - immunology T-Lymphocytes - metabolism TARC |
| title | RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo |
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