A Mandatory Role for STAT4 in IL-12 Induction of Mouse T Cell CCR5
IL-12 was recently shown to induce CCR5 on TCR-triggered mouse T cells. Considering that STAT4 is the most critical of IL-12 signaling molecules, this study investigated the role for STAT4 in the induction of CCR5 expression. IL-12R was induced by stimulation with anti-CD3 plus anti-CD28 mAb similar...
Gespeichert in:
| Veröffentlicht in: | The Journal of immunology (1950) 2001-12, Vol.167 (12), p.6877-6883 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6883 |
|---|---|
| container_issue | 12 |
| container_start_page | 6877 |
| container_title | The Journal of immunology (1950) |
| container_volume | 167 |
| creator | Iwasaki, Masayuki Mukai, Takao Nakajima, Chigusa Yang, Yi-Fu Gao, Ping Yamaguchi, Nobuya Tomura, Michio Fujiwara, Hiromi Hamaoka, Toshiyuki |
| description | IL-12 was recently shown to induce CCR5 on TCR-triggered mouse T cells. Considering that STAT4 is the most critical of IL-12 signaling molecules, this study investigated the role for STAT4 in the induction of CCR5 expression. IL-12R was induced by stimulation with anti-CD3 plus anti-CD28 mAb similarly on T cells from wild-type (WT) and STAT4-deficient (STAT4(-/-)) mice, but the levels of IL-12R induced on IFN-gamma-deficient (IFN-gamma(-/-)) T cells were lower compared with WT T cells. Exposure of TCR-triggered WT T cells to IL-12 induced CCR5 expression. In contrast, TCR-triggered STAT4(-/-) T cells failed to express CCR5 in response to IL-12. IL-12 stimulation induced detectable albeit reduced levels of CCR5 expression on IFN-gamma(-/-) T cells. Addition of rIFN-gamma to cultures of IFN-gamma(-/-) T cells, particularly to cultures during TCR triggering resulted in restoration of CCR5 expression. However, CCR5 expression was not induced in STAT4(-/-) T cells by supplementation of rIFN-gamma. These results indicate that for the induction of CCR5 on T cells, 1) STAT4 plays an indispensable role; 2) such a role is not substituted by simply supplementing rIFN-gamma; and 3) IFN-gamma amplifies CCR5 induction depending on the presence of STAT4. |
| doi_str_mv | 10.4049/jimmunol.167.12.6877 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72342398</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72342398</sourcerecordid><originalsourceid>FETCH-LOGICAL-c413t-694acba94dbb36fcb0b793de037a3bde95223a56365889003dad368b811328f73</originalsourceid><addsrcrecordid>eNqFkEtLw0AYRQdRbK3-A5FZiZvEbx6ZySxr8FFoEWpcD5NkYlOSjGYaSv-9Ka3oztXdnHu5HISuCYQcuLpfV03Tt64OiZAhoaGIpTxBYxJFEAgB4hSNASgNiBRyhC68XwOAAMrP0YgQyVQE0Rg9TPHCtIXZuG6Hl662uHQdfkunKcdVi2fzgFA8a4s-31Suxa7EC9d7i1Oc2LrGSbKMLtFZaWpvr445Qe9Pj2nyEsxfn2fJdB7knLBNIBQ3eWYUL7KMiTLPIJOKFRaYNCwrrIooZSYSTERxrABYYQom4iwmhNG4lGyCbg-7n5376q3f6Kby-fDCtHb4pCVlnDIV_wuSmDBBQQ0gP4B557zvbKk_u6ox3U4T0HvJ-keyHiRrQvVe8lC7Oe73WWOL39LR6gDcHYBV9bHaVp3VvjF1PeBEb7fbv1vfjjuEGQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18136209</pqid></control><display><type>article</type><title>A Mandatory Role for STAT4 in IL-12 Induction of Mouse T Cell CCR5</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Iwasaki, Masayuki ; Mukai, Takao ; Nakajima, Chigusa ; Yang, Yi-Fu ; Gao, Ping ; Yamaguchi, Nobuya ; Tomura, Michio ; Fujiwara, Hiromi ; Hamaoka, Toshiyuki</creator><creatorcontrib>Iwasaki, Masayuki ; Mukai, Takao ; Nakajima, Chigusa ; Yang, Yi-Fu ; Gao, Ping ; Yamaguchi, Nobuya ; Tomura, Michio ; Fujiwara, Hiromi ; Hamaoka, Toshiyuki</creatorcontrib><description>IL-12 was recently shown to induce CCR5 on TCR-triggered mouse T cells. Considering that STAT4 is the most critical of IL-12 signaling molecules, this study investigated the role for STAT4 in the induction of CCR5 expression. IL-12R was induced by stimulation with anti-CD3 plus anti-CD28 mAb similarly on T cells from wild-type (WT) and STAT4-deficient (STAT4(-/-)) mice, but the levels of IL-12R induced on IFN-gamma-deficient (IFN-gamma(-/-)) T cells were lower compared with WT T cells. Exposure of TCR-triggered WT T cells to IL-12 induced CCR5 expression. In contrast, TCR-triggered STAT4(-/-) T cells failed to express CCR5 in response to IL-12. IL-12 stimulation induced detectable albeit reduced levels of CCR5 expression on IFN-gamma(-/-) T cells. Addition of rIFN-gamma to cultures of IFN-gamma(-/-) T cells, particularly to cultures during TCR triggering resulted in restoration of CCR5 expression. However, CCR5 expression was not induced in STAT4(-/-) T cells by supplementation of rIFN-gamma. These results indicate that for the induction of CCR5 on T cells, 1) STAT4 plays an indispensable role; 2) such a role is not substituted by simply supplementing rIFN-gamma; and 3) IFN-gamma amplifies CCR5 induction depending on the presence of STAT4.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.167.12.6877</identifier><identifier>PMID: 11739505</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; CCR5 protein ; Cells, Cultured ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - physiology ; Flow Cytometry ; g-Interferon ; Humans ; Interferon-gamma - genetics ; Interferon-gamma - pharmacology ; Interleukin-12 - pharmacology ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Receptors, Antigen, T-Cell - metabolism ; Receptors, CCR5 - biosynthesis ; Receptors, CCR5 - genetics ; Receptors, Interleukin - biosynthesis ; Receptors, Interleukin - genetics ; Receptors, Interleukin-12 ; RNA, Messenger - biosynthesis ; Signal Transduction ; Stat4 protein ; STAT4 Transcription Factor ; T-Lymphocytes - drug effects ; T-Lymphocytes - immunology ; Trans-Activators - genetics ; Trans-Activators - physiology</subject><ispartof>The Journal of immunology (1950), 2001-12, Vol.167 (12), p.6877-6883</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-694acba94dbb36fcb0b793de037a3bde95223a56365889003dad368b811328f73</citedby><cites>FETCH-LOGICAL-c413t-694acba94dbb36fcb0b793de037a3bde95223a56365889003dad368b811328f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11739505$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwasaki, Masayuki</creatorcontrib><creatorcontrib>Mukai, Takao</creatorcontrib><creatorcontrib>Nakajima, Chigusa</creatorcontrib><creatorcontrib>Yang, Yi-Fu</creatorcontrib><creatorcontrib>Gao, Ping</creatorcontrib><creatorcontrib>Yamaguchi, Nobuya</creatorcontrib><creatorcontrib>Tomura, Michio</creatorcontrib><creatorcontrib>Fujiwara, Hiromi</creatorcontrib><creatorcontrib>Hamaoka, Toshiyuki</creatorcontrib><title>A Mandatory Role for STAT4 in IL-12 Induction of Mouse T Cell CCR5</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>IL-12 was recently shown to induce CCR5 on TCR-triggered mouse T cells. Considering that STAT4 is the most critical of IL-12 signaling molecules, this study investigated the role for STAT4 in the induction of CCR5 expression. IL-12R was induced by stimulation with anti-CD3 plus anti-CD28 mAb similarly on T cells from wild-type (WT) and STAT4-deficient (STAT4(-/-)) mice, but the levels of IL-12R induced on IFN-gamma-deficient (IFN-gamma(-/-)) T cells were lower compared with WT T cells. Exposure of TCR-triggered WT T cells to IL-12 induced CCR5 expression. In contrast, TCR-triggered STAT4(-/-) T cells failed to express CCR5 in response to IL-12. IL-12 stimulation induced detectable albeit reduced levels of CCR5 expression on IFN-gamma(-/-) T cells. Addition of rIFN-gamma to cultures of IFN-gamma(-/-) T cells, particularly to cultures during TCR triggering resulted in restoration of CCR5 expression. However, CCR5 expression was not induced in STAT4(-/-) T cells by supplementation of rIFN-gamma. These results indicate that for the induction of CCR5 on T cells, 1) STAT4 plays an indispensable role; 2) such a role is not substituted by simply supplementing rIFN-gamma; and 3) IFN-gamma amplifies CCR5 induction depending on the presence of STAT4.</description><subject>Animals</subject><subject>CCR5 protein</subject><subject>Cells, Cultured</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Flow Cytometry</subject><subject>g-Interferon</subject><subject>Humans</subject><subject>Interferon-gamma - genetics</subject><subject>Interferon-gamma - pharmacology</subject><subject>Interleukin-12 - pharmacology</subject><subject>Lymphocyte Activation</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Knockout</subject><subject>Receptors, Antigen, T-Cell - metabolism</subject><subject>Receptors, CCR5 - biosynthesis</subject><subject>Receptors, CCR5 - genetics</subject><subject>Receptors, Interleukin - biosynthesis</subject><subject>Receptors, Interleukin - genetics</subject><subject>Receptors, Interleukin-12</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Signal Transduction</subject><subject>Stat4 protein</subject><subject>STAT4 Transcription Factor</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - immunology</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - physiology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLw0AYRQdRbK3-A5FZiZvEbx6ZySxr8FFoEWpcD5NkYlOSjGYaSv-9Ka3oztXdnHu5HISuCYQcuLpfV03Tt64OiZAhoaGIpTxBYxJFEAgB4hSNASgNiBRyhC68XwOAAMrP0YgQyVQE0Rg9TPHCtIXZuG6Hl662uHQdfkunKcdVi2fzgFA8a4s-31Suxa7EC9d7i1Oc2LrGSbKMLtFZaWpvr445Qe9Pj2nyEsxfn2fJdB7knLBNIBQ3eWYUL7KMiTLPIJOKFRaYNCwrrIooZSYSTERxrABYYQom4iwmhNG4lGyCbg-7n5376q3f6Kby-fDCtHb4pCVlnDIV_wuSmDBBQQ0gP4B557zvbKk_u6ox3U4T0HvJ-keyHiRrQvVe8lC7Oe73WWOL39LR6gDcHYBV9bHaVp3VvjF1PeBEb7fbv1vfjjuEGQ</recordid><startdate>20011215</startdate><enddate>20011215</enddate><creator>Iwasaki, Masayuki</creator><creator>Mukai, Takao</creator><creator>Nakajima, Chigusa</creator><creator>Yang, Yi-Fu</creator><creator>Gao, Ping</creator><creator>Yamaguchi, Nobuya</creator><creator>Tomura, Michio</creator><creator>Fujiwara, Hiromi</creator><creator>Hamaoka, Toshiyuki</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><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20011215</creationdate><title>A Mandatory Role for STAT4 in IL-12 Induction of Mouse T Cell CCR5</title><author>Iwasaki, Masayuki ; Mukai, Takao ; Nakajima, Chigusa ; Yang, Yi-Fu ; Gao, Ping ; Yamaguchi, Nobuya ; Tomura, Michio ; Fujiwara, Hiromi ; Hamaoka, Toshiyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-694acba94dbb36fcb0b793de037a3bde95223a56365889003dad368b811328f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>CCR5 protein</topic><topic>Cells, Cultured</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - physiology</topic><topic>Flow Cytometry</topic><topic>g-Interferon</topic><topic>Humans</topic><topic>Interferon-gamma - genetics</topic><topic>Interferon-gamma - pharmacology</topic><topic>Interleukin-12 - pharmacology</topic><topic>Lymphocyte Activation</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Knockout</topic><topic>Receptors, Antigen, T-Cell - metabolism</topic><topic>Receptors, CCR5 - biosynthesis</topic><topic>Receptors, CCR5 - genetics</topic><topic>Receptors, Interleukin - biosynthesis</topic><topic>Receptors, Interleukin - genetics</topic><topic>Receptors, Interleukin-12</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Signal Transduction</topic><topic>Stat4 protein</topic><topic>STAT4 Transcription Factor</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - immunology</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iwasaki, Masayuki</creatorcontrib><creatorcontrib>Mukai, Takao</creatorcontrib><creatorcontrib>Nakajima, Chigusa</creatorcontrib><creatorcontrib>Yang, Yi-Fu</creatorcontrib><creatorcontrib>Gao, Ping</creatorcontrib><creatorcontrib>Yamaguchi, Nobuya</creatorcontrib><creatorcontrib>Tomura, Michio</creatorcontrib><creatorcontrib>Fujiwara, Hiromi</creatorcontrib><creatorcontrib>Hamaoka, Toshiyuki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iwasaki, Masayuki</au><au>Mukai, Takao</au><au>Nakajima, Chigusa</au><au>Yang, Yi-Fu</au><au>Gao, Ping</au><au>Yamaguchi, Nobuya</au><au>Tomura, Michio</au><au>Fujiwara, Hiromi</au><au>Hamaoka, Toshiyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Mandatory Role for STAT4 in IL-12 Induction of Mouse T Cell CCR5</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2001-12-15</date><risdate>2001</risdate><volume>167</volume><issue>12</issue><spage>6877</spage><epage>6883</epage><pages>6877-6883</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>IL-12 was recently shown to induce CCR5 on TCR-triggered mouse T cells. Considering that STAT4 is the most critical of IL-12 signaling molecules, this study investigated the role for STAT4 in the induction of CCR5 expression. IL-12R was induced by stimulation with anti-CD3 plus anti-CD28 mAb similarly on T cells from wild-type (WT) and STAT4-deficient (STAT4(-/-)) mice, but the levels of IL-12R induced on IFN-gamma-deficient (IFN-gamma(-/-)) T cells were lower compared with WT T cells. Exposure of TCR-triggered WT T cells to IL-12 induced CCR5 expression. In contrast, TCR-triggered STAT4(-/-) T cells failed to express CCR5 in response to IL-12. IL-12 stimulation induced detectable albeit reduced levels of CCR5 expression on IFN-gamma(-/-) T cells. Addition of rIFN-gamma to cultures of IFN-gamma(-/-) T cells, particularly to cultures during TCR triggering resulted in restoration of CCR5 expression. However, CCR5 expression was not induced in STAT4(-/-) T cells by supplementation of rIFN-gamma. These results indicate that for the induction of CCR5 on T cells, 1) STAT4 plays an indispensable role; 2) such a role is not substituted by simply supplementing rIFN-gamma; and 3) IFN-gamma amplifies CCR5 induction depending on the presence of STAT4.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>11739505</pmid><doi>10.4049/jimmunol.167.12.6877</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 2001-12, Vol.167 (12), p.6877-6883 |
| issn | 0022-1767 1550-6606 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72342398 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals CCR5 protein Cells, Cultured DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Flow Cytometry g-Interferon Humans Interferon-gamma - genetics Interferon-gamma - pharmacology Interleukin-12 - pharmacology Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Knockout Receptors, Antigen, T-Cell - metabolism Receptors, CCR5 - biosynthesis Receptors, CCR5 - genetics Receptors, Interleukin - biosynthesis Receptors, Interleukin - genetics Receptors, Interleukin-12 RNA, Messenger - biosynthesis Signal Transduction Stat4 protein STAT4 Transcription Factor T-Lymphocytes - drug effects T-Lymphocytes - immunology Trans-Activators - genetics Trans-Activators - physiology |
| title | A Mandatory Role for STAT4 in IL-12 Induction of Mouse T Cell CCR5 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T16%3A46%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Mandatory%20Role%20for%20STAT4%20in%20IL-12%20Induction%20of%20Mouse%20T%20Cell%20CCR5&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Iwasaki,%20Masayuki&rft.date=2001-12-15&rft.volume=167&rft.issue=12&rft.spage=6877&rft.epage=6883&rft.pages=6877-6883&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.167.12.6877&rft_dat=%3Cproquest_cross%3E72342398%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18136209&rft_id=info:pmid/11739505&rfr_iscdi=true |