Impaired development of human Th1 cells in patients with deficient expression of STAT4
IL-12 activates STAT4, which is a critical regulator of inflammation and T helper type I (Th1) lineage development in murine systems. The requirement for STAT4 in the generation of human Th1 cells has not been examined thoroughly. Compared with control Th1 cultures, expression of the Th1 genes IFNγ,...
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| Veröffentlicht in: | Blood 2009-06, Vol.113 (23), p.5887-5890 |
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| creator | Chang, Hua-Chen Han, Ling Goswami, Ritobrata Nguyen, Evelyn T. Pelloso, David Robertson, Michael J. Kaplan, Mark H. |
| description | IL-12 activates STAT4, which is a critical regulator of inflammation and T helper type I (Th1) lineage development in murine systems. The requirement for STAT4 in the generation of human Th1 cells has not been examined thoroughly. Compared with control Th1 cultures, expression of the Th1 genes IFNγ, IL-12Rβ2, and TNFα is greatly reduced in Th1 cultures of CD4 T cells isolated from lymphoma patients after autologous stem cell transplantation who have acquired STAT4 deficiency. Moreover, IL-4 and IL-5 production is increased in patient Th1 cultures though there are no defects in the development of Th2 cells. Reconstitution of STAT4 in patient T cells allowed recovery of IFNγ and IL-12Rβ2 expression, whereas ectopic expression of IL-12Rβ2 did not rescue STAT4 expression, and increased IFNγ production only to levels intermediate between control and patient samples. These results demonstrate that, as in murine systems, STAT4 is required for optimal human Th1 lineage development. |
| doi_str_mv | 10.1182/blood-2008-09-179820 |
| format | Article |
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The requirement for STAT4 in the generation of human Th1 cells has not been examined thoroughly. Compared with control Th1 cultures, expression of the Th1 genes IFNγ, IL-12Rβ2, and TNFα is greatly reduced in Th1 cultures of CD4 T cells isolated from lymphoma patients after autologous stem cell transplantation who have acquired STAT4 deficiency. Moreover, IL-4 and IL-5 production is increased in patient Th1 cultures though there are no defects in the development of Th2 cells. Reconstitution of STAT4 in patient T cells allowed recovery of IFNγ and IL-12Rβ2 expression, whereas ectopic expression of IL-12Rβ2 did not rescue STAT4 expression, and increased IFNγ production only to levels intermediate between control and patient samples. These results demonstrate that, as in murine systems, STAT4 is required for optimal human Th1 lineage development.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2008-09-179820</identifier><identifier>PMID: 19359411</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Analysis of the immune response. Humoral and cellular immunity ; Biological and medical sciences ; Cell Differentiation - immunology ; Cells, Cultured ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; Immunobiology ; Lymphoma - genetics ; Lymphoma - immunology ; Lymphoma - metabolism ; Organs and cells involved in the immune response ; Receptors, Interleukin-12 - metabolism ; STAT4 Transcription Factor - deficiency ; STAT4 Transcription Factor - genetics ; STAT4 Transcription Factor - metabolism ; Th1 Cells - cytology ; Th1 Cells - immunology ; Th1 Cells - metabolism</subject><ispartof>Blood, 2009-06, Vol.113 (23), p.5887-5890</ispartof><rights>2009 American Society of Hematology</rights><rights>2009 INIST-CNRS</rights><rights>2009 by The American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-79f47ce5500dbc269afa3493b27e020426ddb7d5e0f4f8d3f8861f50046300df3</citedby><cites>FETCH-LOGICAL-c491t-79f47ce5500dbc269afa3493b27e020426ddb7d5e0f4f8d3f8861f50046300df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21561551$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19359411$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Hua-Chen</creatorcontrib><creatorcontrib>Han, Ling</creatorcontrib><creatorcontrib>Goswami, Ritobrata</creatorcontrib><creatorcontrib>Nguyen, Evelyn T.</creatorcontrib><creatorcontrib>Pelloso, David</creatorcontrib><creatorcontrib>Robertson, Michael J.</creatorcontrib><creatorcontrib>Kaplan, Mark H.</creatorcontrib><title>Impaired development of human Th1 cells in patients with deficient expression of STAT4</title><title>Blood</title><addtitle>Blood</addtitle><description>IL-12 activates STAT4, which is a critical regulator of inflammation and T helper type I (Th1) lineage development in murine systems. The requirement for STAT4 in the generation of human Th1 cells has not been examined thoroughly. Compared with control Th1 cultures, expression of the Th1 genes IFNγ, IL-12Rβ2, and TNFα is greatly reduced in Th1 cultures of CD4 T cells isolated from lymphoma patients after autologous stem cell transplantation who have acquired STAT4 deficiency. Moreover, IL-4 and IL-5 production is increased in patient Th1 cultures though there are no defects in the development of Th2 cells. Reconstitution of STAT4 in patient T cells allowed recovery of IFNγ and IL-12Rβ2 expression, whereas ectopic expression of IL-12Rβ2 did not rescue STAT4 expression, and increased IFNγ production only to levels intermediate between control and patient samples. These results demonstrate that, as in murine systems, STAT4 is required for optimal human Th1 lineage development.</description><subject>Analysis of the immune response. Humoral and cellular immunity</subject><subject>Biological and medical sciences</subject><subject>Cell Differentiation - immunology</subject><subject>Cells, Cultured</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Humans</subject><subject>Immunobiology</subject><subject>Lymphoma - genetics</subject><subject>Lymphoma - immunology</subject><subject>Lymphoma - metabolism</subject><subject>Organs and cells involved in the immune response</subject><subject>Receptors, Interleukin-12 - metabolism</subject><subject>STAT4 Transcription Factor - deficiency</subject><subject>STAT4 Transcription Factor - genetics</subject><subject>STAT4 Transcription Factor - metabolism</subject><subject>Th1 Cells - cytology</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - metabolism</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v1DAQxS0EokvhGyCUC9wC439JfEGqqkIrVeLAwtVy7DFrlMTBzm7h2-OwqxYunCx7fm88bx4hLym8pbRj7_ohRlczgK4GVdNWdQwekQ2VrDwAg8dkAwBNLVRLz8iznL8DUMGZfErOqOJSCUo35OvNOJuQ0FUODzjEecRpqaKvdvvRTNV2RyuLw5CrMFWzWUKp5uouLLvC-2DXe4U_54Q5hzitws_bi614Tp54M2R8cTrPyZcPV9vL6_r208eby4vb2gpFl7pVXrQWpQRwvWWNMt5woXjPWiwWBGuc61snEbzwneO-6xrqCy0aXiSen5P3x77zvh_R2TJOMoOeUxhN-qWjCfrfyhR2-ls8aNYCcCZKgzenBin-2GNe9Bjy6thMGPdZNy1nZVeqgOII2hRzTujvP6Gg10D0n0D0GogGpY-BFNmrvwd8EJ0SKMDrE2CyNYNPZrIh33OMyoZKSR-cYlnnIWDSed2-RVfSs4t2Mfx_kt8R-aqS</recordid><startdate>20090604</startdate><enddate>20090604</enddate><creator>Chang, Hua-Chen</creator><creator>Han, Ling</creator><creator>Goswami, Ritobrata</creator><creator>Nguyen, Evelyn T.</creator><creator>Pelloso, David</creator><creator>Robertson, Michael J.</creator><creator>Kaplan, Mark H.</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>5PM</scope></search><sort><creationdate>20090604</creationdate><title>Impaired development of human Th1 cells in patients with deficient expression of STAT4</title><author>Chang, Hua-Chen ; Han, Ling ; Goswami, Ritobrata ; Nguyen, Evelyn T. ; Pelloso, David ; Robertson, Michael J. ; Kaplan, Mark H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-79f47ce5500dbc269afa3493b27e020426ddb7d5e0f4f8d3f8861f50046300df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Analysis of the immune response. Humoral and cellular immunity</topic><topic>Biological and medical sciences</topic><topic>Cell Differentiation - immunology</topic><topic>Cells, Cultured</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Humans</topic><topic>Immunobiology</topic><topic>Lymphoma - genetics</topic><topic>Lymphoma - immunology</topic><topic>Lymphoma - metabolism</topic><topic>Organs and cells involved in the immune response</topic><topic>Receptors, Interleukin-12 - metabolism</topic><topic>STAT4 Transcription Factor - deficiency</topic><topic>STAT4 Transcription Factor - genetics</topic><topic>STAT4 Transcription Factor - metabolism</topic><topic>Th1 Cells - cytology</topic><topic>Th1 Cells - immunology</topic><topic>Th1 Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Hua-Chen</creatorcontrib><creatorcontrib>Han, Ling</creatorcontrib><creatorcontrib>Goswami, Ritobrata</creatorcontrib><creatorcontrib>Nguyen, Evelyn T.</creatorcontrib><creatorcontrib>Pelloso, David</creatorcontrib><creatorcontrib>Robertson, Michael J.</creatorcontrib><creatorcontrib>Kaplan, Mark H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><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>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Hua-Chen</au><au>Han, Ling</au><au>Goswami, Ritobrata</au><au>Nguyen, Evelyn T.</au><au>Pelloso, David</au><au>Robertson, Michael J.</au><au>Kaplan, Mark H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired development of human Th1 cells in patients with deficient expression of STAT4</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2009-06-04</date><risdate>2009</risdate><volume>113</volume><issue>23</issue><spage>5887</spage><epage>5890</epage><pages>5887-5890</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>IL-12 activates STAT4, which is a critical regulator of inflammation and T helper type I (Th1) lineage development in murine systems. The requirement for STAT4 in the generation of human Th1 cells has not been examined thoroughly. Compared with control Th1 cultures, expression of the Th1 genes IFNγ, IL-12Rβ2, and TNFα is greatly reduced in Th1 cultures of CD4 T cells isolated from lymphoma patients after autologous stem cell transplantation who have acquired STAT4 deficiency. Moreover, IL-4 and IL-5 production is increased in patient Th1 cultures though there are no defects in the development of Th2 cells. Reconstitution of STAT4 in patient T cells allowed recovery of IFNγ and IL-12Rβ2 expression, whereas ectopic expression of IL-12Rβ2 did not rescue STAT4 expression, and increased IFNγ production only to levels intermediate between control and patient samples. These results demonstrate that, as in murine systems, STAT4 is required for optimal human Th1 lineage development.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>19359411</pmid><doi>10.1182/blood-2008-09-179820</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis of the immune response. Humoral and cellular immunity Biological and medical sciences Cell Differentiation - immunology Cells, Cultured Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Immunobiology Lymphoma - genetics Lymphoma - immunology Lymphoma - metabolism Organs and cells involved in the immune response Receptors, Interleukin-12 - metabolism STAT4 Transcription Factor - deficiency STAT4 Transcription Factor - genetics STAT4 Transcription Factor - metabolism Th1 Cells - cytology Th1 Cells - immunology Th1 Cells - metabolism |
| title | Impaired development of human Th1 cells in patients with deficient expression of STAT4 |
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