Notch Regulates Cytolytic Effector Function in CD8+ T Cells
The maturation of naive CD8(+) T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecul...
Gespeichert in:
| Veröffentlicht in: | The Journal of immunology (1950) 2009-03, Vol.182 (6), p.3380-3389 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3389 |
|---|---|
| container_issue | 6 |
| container_start_page | 3380 |
| container_title | The Journal of immunology (1950) |
| container_volume | 182 |
| creator | Cho, Ok Hyun Shin, Hyun Mu Miele, Lucio Golde, Todd E Fauq, Abdul Minter, Lisa M Osborne, Barbara A |
| description | The maturation of naive CD8(+) T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8(+) effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B. |
| doi_str_mv | 10.4049/jimmunol.0802598 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_4049_jimmunol_0802598</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>19265115</sourcerecordid><originalsourceid>FETCH-LOGICAL-c371t-f98c39d7e6376c5c5759d4fefe96d1dd57a88a0dc8c4858d23ba2d469a1927aa3</originalsourceid><addsrcrecordid>eNpFkM9LwzAUgIMobk7vniQ3D9L5kja_8CR1U2EoyDyHLEm3jnQdTUvZf29lE0_v8n2P9z6EbglMM8jU47asqm5XhylIoEzJMzQmjEHCOfBzNAagNCGCixG6inELABxodolGRFHOCGFj9PRRt3aDv_y6C6b1EeeHtg6HtrR4VhTetnWD593OtmW9w-UO5y_yAS9x7kOI1-iiMCH6m9OcoO_5bJm_JYvP1_f8eZHYVJA2KZS0qXLC81RwyywTTLms8IVX3BHnmDBSGnBW2kwy6Wi6MtRlXJnhTGFMOkFw3GubOsbGF3rflJVpDpqA_u2g_zroU4dBuTsq-25VefcvnB4fgPsjsCnXm75svI6VCWHAie77nkiquU5TCekPKTZntQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Notch Regulates Cytolytic Effector Function in CD8+ T Cells</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Cho, Ok Hyun ; Shin, Hyun Mu ; Miele, Lucio ; Golde, Todd E ; Fauq, Abdul ; Minter, Lisa M ; Osborne, Barbara A</creator><creatorcontrib>Cho, Ok Hyun ; Shin, Hyun Mu ; Miele, Lucio ; Golde, Todd E ; Fauq, Abdul ; Minter, Lisa M ; Osborne, Barbara A</creatorcontrib><description>The maturation of naive CD8(+) T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8(+) effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.0802598</identifier><identifier>PMID: 19265115</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Amyloid Precursor Protein Secretases - antagonists & inhibitors ; Amyloid Precursor Protein Secretases - physiology ; Animals ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell Differentiation - immunology ; Cytotoxicity, Immunologic ; Granzymes - antagonists & inhibitors ; Granzymes - genetics ; Granzymes - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Perforin - antagonists & inhibitors ; Perforin - genetics ; Perforin - metabolism ; Promoter Regions, Genetic - immunology ; Protein Binding - immunology ; Receptor, Notch1 - antagonists & inhibitors ; Receptor, Notch1 - metabolism ; Receptor, Notch1 - physiology ; Signal Transduction - genetics ; Signal Transduction - immunology ; T-Box Domain Proteins - antagonists & inhibitors ; T-Box Domain Proteins - genetics ; T-Box Domain Proteins - metabolism ; T-Lymphocytes, Cytotoxic - cytology ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - metabolism</subject><ispartof>The Journal of immunology (1950), 2009-03, Vol.182 (6), p.3380-3389</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-f98c39d7e6376c5c5759d4fefe96d1dd57a88a0dc8c4858d23ba2d469a1927aa3</citedby><cites>FETCH-LOGICAL-c371t-f98c39d7e6376c5c5759d4fefe96d1dd57a88a0dc8c4858d23ba2d469a1927aa3</cites></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/19265115$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cho, Ok Hyun</creatorcontrib><creatorcontrib>Shin, Hyun Mu</creatorcontrib><creatorcontrib>Miele, Lucio</creatorcontrib><creatorcontrib>Golde, Todd E</creatorcontrib><creatorcontrib>Fauq, Abdul</creatorcontrib><creatorcontrib>Minter, Lisa M</creatorcontrib><creatorcontrib>Osborne, Barbara A</creatorcontrib><title>Notch Regulates Cytolytic Effector Function in CD8+ T Cells</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>The maturation of naive CD8(+) T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8(+) effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.</description><subject>Amyloid Precursor Protein Secretases - antagonists & inhibitors</subject><subject>Amyloid Precursor Protein Secretases - physiology</subject><subject>Animals</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell Differentiation - immunology</subject><subject>Cytotoxicity, Immunologic</subject><subject>Granzymes - antagonists & inhibitors</subject><subject>Granzymes - genetics</subject><subject>Granzymes - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Perforin - antagonists & inhibitors</subject><subject>Perforin - genetics</subject><subject>Perforin - metabolism</subject><subject>Promoter Regions, Genetic - immunology</subject><subject>Protein Binding - immunology</subject><subject>Receptor, Notch1 - antagonists & inhibitors</subject><subject>Receptor, Notch1 - metabolism</subject><subject>Receptor, Notch1 - physiology</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - immunology</subject><subject>T-Box Domain Proteins - antagonists & inhibitors</subject><subject>T-Box Domain Proteins - genetics</subject><subject>T-Box Domain Proteins - metabolism</subject><subject>T-Lymphocytes, Cytotoxic - cytology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM9LwzAUgIMobk7vniQ3D9L5kja_8CR1U2EoyDyHLEm3jnQdTUvZf29lE0_v8n2P9z6EbglMM8jU47asqm5XhylIoEzJMzQmjEHCOfBzNAagNCGCixG6inELABxodolGRFHOCGFj9PRRt3aDv_y6C6b1EeeHtg6HtrR4VhTetnWD593OtmW9w-UO5y_yAS9x7kOI1-iiMCH6m9OcoO_5bJm_JYvP1_f8eZHYVJA2KZS0qXLC81RwyywTTLms8IVX3BHnmDBSGnBW2kwy6Wi6MtRlXJnhTGFMOkFw3GubOsbGF3rflJVpDpqA_u2g_zroU4dBuTsq-25VefcvnB4fgPsjsCnXm75svI6VCWHAie77nkiquU5TCekPKTZntQ</recordid><startdate>20090315</startdate><enddate>20090315</enddate><creator>Cho, Ok Hyun</creator><creator>Shin, Hyun Mu</creator><creator>Miele, Lucio</creator><creator>Golde, Todd E</creator><creator>Fauq, Abdul</creator><creator>Minter, Lisa M</creator><creator>Osborne, Barbara A</creator><general>Am Assoc Immnol</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></search><sort><creationdate>20090315</creationdate><title>Notch Regulates Cytolytic Effector Function in CD8+ T Cells</title><author>Cho, Ok Hyun ; Shin, Hyun Mu ; Miele, Lucio ; Golde, Todd E ; Fauq, Abdul ; Minter, Lisa M ; Osborne, Barbara A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-f98c39d7e6376c5c5759d4fefe96d1dd57a88a0dc8c4858d23ba2d469a1927aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Amyloid Precursor Protein Secretases - antagonists & inhibitors</topic><topic>Amyloid Precursor Protein Secretases - physiology</topic><topic>Animals</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell Differentiation - immunology</topic><topic>Cytotoxicity, Immunologic</topic><topic>Granzymes - antagonists & inhibitors</topic><topic>Granzymes - genetics</topic><topic>Granzymes - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Perforin - antagonists & inhibitors</topic><topic>Perforin - genetics</topic><topic>Perforin - metabolism</topic><topic>Promoter Regions, Genetic - immunology</topic><topic>Protein Binding - immunology</topic><topic>Receptor, Notch1 - antagonists & inhibitors</topic><topic>Receptor, Notch1 - metabolism</topic><topic>Receptor, Notch1 - physiology</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - immunology</topic><topic>T-Box Domain Proteins - antagonists & inhibitors</topic><topic>T-Box Domain Proteins - genetics</topic><topic>T-Box Domain Proteins - metabolism</topic><topic>T-Lymphocytes, Cytotoxic - cytology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cho, Ok Hyun</creatorcontrib><creatorcontrib>Shin, Hyun Mu</creatorcontrib><creatorcontrib>Miele, Lucio</creatorcontrib><creatorcontrib>Golde, Todd E</creatorcontrib><creatorcontrib>Fauq, Abdul</creatorcontrib><creatorcontrib>Minter, Lisa M</creatorcontrib><creatorcontrib>Osborne, Barbara A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cho, Ok Hyun</au><au>Shin, Hyun Mu</au><au>Miele, Lucio</au><au>Golde, Todd E</au><au>Fauq, Abdul</au><au>Minter, Lisa M</au><au>Osborne, Barbara A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Notch Regulates Cytolytic Effector Function in CD8+ T Cells</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2009-03-15</date><risdate>2009</risdate><volume>182</volume><issue>6</issue><spage>3380</spage><epage>3389</epage><pages>3380-3389</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>The maturation of naive CD8(+) T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8(+) effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>19265115</pmid><doi>10.4049/jimmunol.0802598</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 2009-03, Vol.182 (6), p.3380-3389 |
| issn | 0022-1767 1550-6606 |
| language | eng |
| recordid | cdi_crossref_primary_10_4049_jimmunol_0802598 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - physiology Animals CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Differentiation - immunology Cytotoxicity, Immunologic Granzymes - antagonists & inhibitors Granzymes - genetics Granzymes - metabolism Mice Mice, Inbred C57BL Mice, Transgenic Perforin - antagonists & inhibitors Perforin - genetics Perforin - metabolism Promoter Regions, Genetic - immunology Protein Binding - immunology Receptor, Notch1 - antagonists & inhibitors Receptor, Notch1 - metabolism Receptor, Notch1 - physiology Signal Transduction - genetics Signal Transduction - immunology T-Box Domain Proteins - antagonists & inhibitors T-Box Domain Proteins - genetics T-Box Domain Proteins - metabolism T-Lymphocytes, Cytotoxic - cytology T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism |
| title | Notch Regulates Cytolytic Effector Function in CD8+ T Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T18%3A37%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Notch%20Regulates%20Cytolytic%20Effector%20Function%20in%20CD8+%20T%20Cells&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Cho,%20Ok%20Hyun&rft.date=2009-03-15&rft.volume=182&rft.issue=6&rft.spage=3380&rft.epage=3389&rft.pages=3380-3389&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.0802598&rft_dat=%3Cpubmed_cross%3E19265115%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/19265115&rfr_iscdi=true |