Transcriptome profiling of human FoxP3+ regulatory T cells
Abstract The major goal of this study was to perform an in depth characterization of the “gene signature” of human FoxP3+ T regulatory cells (Tregs). Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro , were analy...
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| Veröffentlicht in: | Human immunology 2016-02, Vol.77 (2), p.201-213 |
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| creator | Bhairavabhotla, Ravikiran Kim, Yong C Glass, Deborah D Escobar, Thelma M Patel, Mira C Zahr, Rami Nguyen, Cuong K Kilaru, Gokhul K Muljo, Stefan A Shevach, Ethan M |
| description | Abstract The major goal of this study was to perform an in depth characterization of the “gene signature” of human FoxP3+ T regulatory cells (Tregs). Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro , were analyzed via RNA sequencing (RNA-seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3 , IKZF2 , and CTLA4 in Tregs. Notably, a number of yet uncharacterized genes ( RTKN2 , LAYN , UTS2 , CSF2RB , TRIB1 , F5 , CECAM4 , CD70 , ENC1 and NKG7 ) were identified and validated as being differentially expressed in human Tregs. We further characterize the functional roles of RTKN2 and LAYN by analyzing their roles in vitro human Treg suppression assays by knocking them down in Tregs and overexpressing them in Tconvs. In order to facilitate a better understanding of the human Treg gene expression signature, we have generated from our results a hypothetical interactome of genes and miRNAs in Tregs and Tconvs. |
| doi_str_mv | 10.1016/j.humimm.2015.12.004 |
| format | Article |
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Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro , were analyzed via RNA sequencing (RNA-seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3 , IKZF2 , and CTLA4 in Tregs. Notably, a number of yet uncharacterized genes ( RTKN2 , LAYN , UTS2 , CSF2RB , TRIB1 , F5 , CECAM4 , CD70 , ENC1 and NKG7 ) were identified and validated as being differentially expressed in human Tregs. We further characterize the functional roles of RTKN2 and LAYN by analyzing their roles in vitro human Treg suppression assays by knocking them down in Tregs and overexpressing them in Tconvs. In order to facilitate a better understanding of the human Treg gene expression signature, we have generated from our results a hypothetical interactome of genes and miRNAs in Tregs and Tconvs.</description><identifier>ISSN: 0198-8859</identifier><identifier>ISSN: 1879-1166</identifier><identifier>EISSN: 1879-1166</identifier><identifier>DOI: 10.1016/j.humimm.2015.12.004</identifier><identifier>PMID: 26686412</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Allergy and Immunology ; Cells, Cultured ; Differentially expressed ; Forkhead Transcription Factors - metabolism ; FoxP3 ; Gene Regulatory Networks ; Gene signature ; Humans ; Immune Tolerance - genetics ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; LAYN ; Lectins, C-Type - genetics ; Lectins, C-Type - metabolism ; MicroRNAs - genetics ; MiR-146a ; MiR-146b ; MiR-21 ; MiRNA ; nCounter analysis ; PNA ; RNA sequencing ; RNA, Small Interfering - genetics ; RTKN2 ; Suppressive cells ; T-Lymphocyte Subsets - immunology ; T-Lymphocytes, Regulatory - immunology ; Transcriptome</subject><ispartof>Human immunology, 2016-02, Vol.77 (2), p.201-213</ispartof><rights>2015</rights><rights>Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c621t-15004c81e105a131043bcaaa41796f871a763847b57cb97e2ad55d7edc77c4043</citedby><cites>FETCH-LOGICAL-c621t-15004c81e105a131043bcaaa41796f871a763847b57cb97e2ad55d7edc77c4043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0198885915005844$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26686412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhairavabhotla, Ravikiran</creatorcontrib><creatorcontrib>Kim, Yong C</creatorcontrib><creatorcontrib>Glass, Deborah D</creatorcontrib><creatorcontrib>Escobar, Thelma M</creatorcontrib><creatorcontrib>Patel, Mira C</creatorcontrib><creatorcontrib>Zahr, Rami</creatorcontrib><creatorcontrib>Nguyen, Cuong K</creatorcontrib><creatorcontrib>Kilaru, Gokhul K</creatorcontrib><creatorcontrib>Muljo, Stefan A</creatorcontrib><creatorcontrib>Shevach, Ethan M</creatorcontrib><title>Transcriptome profiling of human FoxP3+ regulatory T cells</title><title>Human immunology</title><addtitle>Hum Immunol</addtitle><description>Abstract The major goal of this study was to perform an in depth characterization of the “gene signature” of human FoxP3+ T regulatory cells (Tregs). Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro , were analyzed via RNA sequencing (RNA-seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3 , IKZF2 , and CTLA4 in Tregs. Notably, a number of yet uncharacterized genes ( RTKN2 , LAYN , UTS2 , CSF2RB , TRIB1 , F5 , CECAM4 , CD70 , ENC1 and NKG7 ) were identified and validated as being differentially expressed in human Tregs. We further characterize the functional roles of RTKN2 and LAYN by analyzing their roles in vitro human Treg suppression assays by knocking them down in Tregs and overexpressing them in Tconvs. In order to facilitate a better understanding of the human Treg gene expression signature, we have generated from our results a hypothetical interactome of genes and miRNAs in Tregs and Tconvs.</description><subject>Allergy and Immunology</subject><subject>Cells, Cultured</subject><subject>Differentially expressed</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>FoxP3</subject><subject>Gene Regulatory Networks</subject><subject>Gene signature</subject><subject>Humans</subject><subject>Immune Tolerance - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>LAYN</subject><subject>Lectins, C-Type - genetics</subject><subject>Lectins, C-Type - metabolism</subject><subject>MicroRNAs - genetics</subject><subject>MiR-146a</subject><subject>MiR-146b</subject><subject>MiR-21</subject><subject>MiRNA</subject><subject>nCounter analysis</subject><subject>PNA</subject><subject>RNA sequencing</subject><subject>RNA, Small Interfering - genetics</subject><subject>RTKN2</subject><subject>Suppressive cells</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Transcriptome</subject><issn>0198-8859</issn><issn>1879-1166</issn><issn>1879-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkltv1DAQhS0EotvCP0Aoj0gowZP4Fh6QqooWpEogsTyPvM5k6yWJFzup2H9PwpZyeYEnS_aZ4znzDWPPgBfAQb3aFTdT7_u-KDnIAsqCc_GArcDoOgdQ6iFbcahNboysT9hpSjvOueZaPGYnpVJGCShX7PU62iG56Pdj6Cnbx9D6zg_bLLTZ7G-H7DJ8-1i9zCJtp86OIR6ydeao69IT9qi1XaKnd-cZ-3z5dn3xLr_-cPX-4vw6d6qEMQc5N-YMEHBpoQIuqo2z1grQtWqNBqtVZYTeSO02tabSNlI2mhqntROz-oy9Ofrup00_X9MwRtvhPvrexgMG6_HPl8Hf4DbcotAKJCwGL-4MYvg6URqx92mJYAcKU0LQykhT1WD-R6q50rXms1QcpS6GlCK19x0Bx4UQ7vBICBdCCCXyH2me_57mvugnkl9xaZ7praeIyXkaHDU-khuxCf5fP_xt4Gai3tnuCx0o7cIUh5kXAqa5AD8tW7IsyQJKGiGq70FUuCU</recordid><startdate>20160201</startdate><enddate>20160201</enddate><creator>Bhairavabhotla, Ravikiran</creator><creator>Kim, Yong C</creator><creator>Glass, Deborah D</creator><creator>Escobar, Thelma M</creator><creator>Patel, Mira C</creator><creator>Zahr, Rami</creator><creator>Nguyen, Cuong K</creator><creator>Kilaru, Gokhul K</creator><creator>Muljo, Stefan A</creator><creator>Shevach, Ethan M</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><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20160201</creationdate><title>Transcriptome profiling of human FoxP3+ regulatory T cells</title><author>Bhairavabhotla, Ravikiran ; Kim, Yong C ; Glass, Deborah D ; Escobar, Thelma M ; Patel, Mira C ; Zahr, Rami ; Nguyen, Cuong K ; Kilaru, Gokhul K ; Muljo, Stefan A ; Shevach, Ethan M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c621t-15004c81e105a131043bcaaa41796f871a763847b57cb97e2ad55d7edc77c4043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Allergy and Immunology</topic><topic>Cells, Cultured</topic><topic>Differentially expressed</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>FoxP3</topic><topic>Gene Regulatory Networks</topic><topic>Gene signature</topic><topic>Humans</topic><topic>Immune Tolerance - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>LAYN</topic><topic>Lectins, C-Type - genetics</topic><topic>Lectins, C-Type - metabolism</topic><topic>MicroRNAs - genetics</topic><topic>MiR-146a</topic><topic>MiR-146b</topic><topic>MiR-21</topic><topic>MiRNA</topic><topic>nCounter analysis</topic><topic>PNA</topic><topic>RNA sequencing</topic><topic>RNA, Small Interfering - genetics</topic><topic>RTKN2</topic><topic>Suppressive cells</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bhairavabhotla, Ravikiran</creatorcontrib><creatorcontrib>Kim, Yong C</creatorcontrib><creatorcontrib>Glass, Deborah D</creatorcontrib><creatorcontrib>Escobar, Thelma M</creatorcontrib><creatorcontrib>Patel, Mira C</creatorcontrib><creatorcontrib>Zahr, Rami</creatorcontrib><creatorcontrib>Nguyen, Cuong K</creatorcontrib><creatorcontrib>Kilaru, Gokhul K</creatorcontrib><creatorcontrib>Muljo, Stefan A</creatorcontrib><creatorcontrib>Shevach, Ethan M</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bhairavabhotla, Ravikiran</au><au>Kim, Yong C</au><au>Glass, Deborah D</au><au>Escobar, Thelma M</au><au>Patel, Mira C</au><au>Zahr, Rami</au><au>Nguyen, Cuong K</au><au>Kilaru, Gokhul K</au><au>Muljo, Stefan A</au><au>Shevach, Ethan M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptome profiling of human FoxP3+ regulatory T cells</atitle><jtitle>Human immunology</jtitle><addtitle>Hum Immunol</addtitle><date>2016-02-01</date><risdate>2016</risdate><volume>77</volume><issue>2</issue><spage>201</spage><epage>213</epage><pages>201-213</pages><issn>0198-8859</issn><issn>1879-1166</issn><eissn>1879-1166</eissn><abstract>Abstract The major goal of this study was to perform an in depth characterization of the “gene signature” of human FoxP3+ T regulatory cells (Tregs). Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro , were analyzed via RNA sequencing (RNA-seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3 , IKZF2 , and CTLA4 in Tregs. Notably, a number of yet uncharacterized genes ( RTKN2 , LAYN , UTS2 , CSF2RB , TRIB1 , F5 , CECAM4 , CD70 , ENC1 and NKG7 ) were identified and validated as being differentially expressed in human Tregs. We further characterize the functional roles of RTKN2 and LAYN by analyzing their roles in vitro human Treg suppression assays by knocking them down in Tregs and overexpressing them in Tconvs. In order to facilitate a better understanding of the human Treg gene expression signature, we have generated from our results a hypothetical interactome of genes and miRNAs in Tregs and Tconvs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26686412</pmid><doi>10.1016/j.humimm.2015.12.004</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Human immunology, 2016-02, Vol.77 (2), p.201-213 |
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| subjects | Allergy and Immunology Cells, Cultured Differentially expressed Forkhead Transcription Factors - metabolism FoxP3 Gene Regulatory Networks Gene signature Humans Immune Tolerance - genetics Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism LAYN Lectins, C-Type - genetics Lectins, C-Type - metabolism MicroRNAs - genetics MiR-146a MiR-146b MiR-21 MiRNA nCounter analysis PNA RNA sequencing RNA, Small Interfering - genetics RTKN2 Suppressive cells T-Lymphocyte Subsets - immunology T-Lymphocytes, Regulatory - immunology Transcriptome |
| title | Transcriptome profiling of human FoxP3+ regulatory T cells |
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