The inhibitory cytokine IL-35 contributes to regulatory T-cell function
Regulatory T (T(reg)) cells are a critical sub-population of CD4+ T cells that are essential for maintaining self tolerance and preventing autoimmunity, for limiting chronic inflammatory diseases, such as asthma and inflammatory bowel disease, and for regulating homeostatic lymphocyte expansion. How...
Gespeichert in:
| Veröffentlicht in: | Nature 2007-11, Vol.450 (7169), p.566-569 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 569 |
|---|---|
| container_issue | 7169 |
| container_start_page | 566 |
| container_title | Nature |
| container_volume | 450 |
| creator | COLLISON, Lauren W WORKMAN, Creg J KUO, Timothy T BOYD, Kelli YAO WANG VIGNALI, Kate M CROSS, Richard SEHY, David BLUMBERG, Richard S VIGNALI, Dario A. A |
| description | Regulatory T (T(reg)) cells are a critical sub-population of CD4+ T cells that are essential for maintaining self tolerance and preventing autoimmunity, for limiting chronic inflammatory diseases, such as asthma and inflammatory bowel disease, and for regulating homeostatic lymphocyte expansion. However, they also suppress natural immune responses to parasites and viruses as well as anti-tumour immunity induced by therapeutic vaccines. Although the manipulation of T(reg) function is an important goal of immunotherapy, the molecules that mediate their suppressive activity remain largely unknown. Here we demonstrate that Epstein-Barr-virus-induced gene 3 (Ebi3, which encodes IL-27beta) and interleukin-12 alpha (Il12a, which encodes IL-12alpha/p35) are highly expressed by mouse Foxp3+ (forkhead box P3) T(reg) cells but not by resting or activated effector CD4+ T (T(eff)) cells, and that an Ebi3-IL-12alpha heterodimer is constitutively secreted by T(reg) but not T(eff) cells. Both Ebi3 and Il12a messenger RNA are markedly upregulated in T(reg) cells co-cultured with T(eff) cells, thereby boosting Ebi3 and IL-12alpha production in trans. T(reg)-cell restriction of this cytokine occurs because Ebi3 is a downstream target of Foxp3, a transcription factor that is required for T(reg)-cell development and function. Ebi3-/- and Il12a-/- T(reg) cells have significantly reduced regulatory activity in vitro and fail to control homeostatic proliferation and to cure inflammatory bowel disease in vivo. Because these phenotypic characteristics are distinct from those of other IL-12 family members, this novel Ebi3-IL-12alpha heterodimeric cytokine has been designated interleukin-35 (IL-35). Ectopic expression of IL-35 confers regulatory activity on naive T cells, whereas recombinant IL-35 suppresses T-cell proliferation. Taken together, these data identify IL-35 as a novel inhibitory cytokine that may be specifically produced by T(reg) cells and is required for maximal suppressive activity. |
| doi_str_mv | 10.1038/nature06306 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_743509529</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A193477433</galeid><sourcerecordid>A193477433</sourcerecordid><originalsourceid>FETCH-LOGICAL-c859t-91b8b6e7ba09ddfbb03ed00fbe51213c393e88ab34849b0cce091b4de606ebd93</originalsourceid><addsrcrecordid>eNqN0_GL0zAUB_AiijdPf_J3KYKKSM-Xpk2TH8fQczAUdOKPJUlfdzm7dJek4P57M2-wTe_c6A-F8nnfvjzykuQ5gQsClL-3MgwOgVFgD5IRKSqWFYxXD5MRQM4z4JSdJU-8vwaAklTF4-SMcKCUAoySy_kVpsZeGWVC79apXof-p7GYTmcZLVPd2-CMGgL6NPSpw8XQyT9wnmnsurQdrA6mt0-TR63sPD7bvs-T7x8_zCefstmXy-lkPMs0L0XIBFFcMayUBNE0rVJAsQFoFZYkJ1RTQZFzqWjBC6FAa4RYUjTIgKFqBD1P3tzmrlx_M6AP9dL4TSfSYj_4uipoCaLMN_L1fyXjJRVAqqOQsjyOixVHYU7idHlVHoVEcF5ygAhf_gWv-8HZOMA6h6JkNPYYUXaLFrLD2ti2D07qBVp0susttiZ-HhNBiyqe_mTPRWxWlNWuiQOvV-am3g-9H-0lXdyB4tPg0ug7Wz2tYO8Pbw8KNvcTf4WFHLyvp9--HoYftXu57-634_mPyefD5BP0v9na9d47bOuVM0vp1jWBerPB9d4GR_1ieyUGtcRmZ7crG8GrLZBey6510mrjd07QKm6RoL8BrBdFjg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>204563853</pqid></control><display><type>article</type><title>The inhibitory cytokine IL-35 contributes to regulatory T-cell function</title><source>MEDLINE</source><source>Nature</source><source>Alma/SFX Local Collection</source><creator>COLLISON, Lauren W ; WORKMAN, Creg J ; KUO, Timothy T ; BOYD, Kelli ; YAO WANG ; VIGNALI, Kate M ; CROSS, Richard ; SEHY, David ; BLUMBERG, Richard S ; VIGNALI, Dario A. A</creator><creatorcontrib>COLLISON, Lauren W ; WORKMAN, Creg J ; KUO, Timothy T ; BOYD, Kelli ; YAO WANG ; VIGNALI, Kate M ; CROSS, Richard ; SEHY, David ; BLUMBERG, Richard S ; VIGNALI, Dario A. A</creatorcontrib><description>Regulatory T (T(reg)) cells are a critical sub-population of CD4+ T cells that are essential for maintaining self tolerance and preventing autoimmunity, for limiting chronic inflammatory diseases, such as asthma and inflammatory bowel disease, and for regulating homeostatic lymphocyte expansion. However, they also suppress natural immune responses to parasites and viruses as well as anti-tumour immunity induced by therapeutic vaccines. Although the manipulation of T(reg) function is an important goal of immunotherapy, the molecules that mediate their suppressive activity remain largely unknown. Here we demonstrate that Epstein-Barr-virus-induced gene 3 (Ebi3, which encodes IL-27beta) and interleukin-12 alpha (Il12a, which encodes IL-12alpha/p35) are highly expressed by mouse Foxp3+ (forkhead box P3) T(reg) cells but not by resting or activated effector CD4+ T (T(eff)) cells, and that an Ebi3-IL-12alpha heterodimer is constitutively secreted by T(reg) but not T(eff) cells. Both Ebi3 and Il12a messenger RNA are markedly upregulated in T(reg) cells co-cultured with T(eff) cells, thereby boosting Ebi3 and IL-12alpha production in trans. T(reg)-cell restriction of this cytokine occurs because Ebi3 is a downstream target of Foxp3, a transcription factor that is required for T(reg)-cell development and function. Ebi3-/- and Il12a-/- T(reg) cells have significantly reduced regulatory activity in vitro and fail to control homeostatic proliferation and to cure inflammatory bowel disease in vivo. Because these phenotypic characteristics are distinct from those of other IL-12 family members, this novel Ebi3-IL-12alpha heterodimeric cytokine has been designated interleukin-35 (IL-35). Ectopic expression of IL-35 confers regulatory activity on naive T cells, whereas recombinant IL-35 suppresses T-cell proliferation. Taken together, these data identify IL-35 as a novel inhibitory cytokine that may be specifically produced by T(reg) cells and is required for maximal suppressive activity.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/nature06306</identifier><identifier>PMID: 18033300</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Animals ; Asthma ; Biological and medical sciences ; Cell Line ; Cell Proliferation ; Cellular biology ; Cytokines ; Disease Models, Animal ; Flow Cytometry ; Forkhead Transcription Factors - metabolism ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene expression ; Gene Expression Regulation ; Genetics of the immune response ; Humans ; Immunobiology ; Immunology ; Immunotherapy ; Inflammatory Bowel Diseases - metabolism ; Interleukin-12 Subunit p35 - deficiency ; Interleukin-12 Subunit p35 - genetics ; Interleukin-12 Subunit p35 - metabolism ; Lymphocytes ; Mice ; Mice, Inbred C57BL ; Minor Histocompatibility Antigens ; Molecular biology ; Parasites ; Receptors, Cytokine - deficiency ; Receptors, Cytokine - genetics ; Receptors, Cytokine - metabolism ; T-Lymphocytes, Regulatory - cytology ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism ; T-Lymphocytes, Regulatory - transplantation ; Vaccines ; Viruses</subject><ispartof>Nature, 2007-11, Vol.450 (7169), p.566-569</ispartof><rights>2008 INIST-CNRS</rights><rights>COPYRIGHT 2007 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Nov 22, 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c859t-91b8b6e7ba09ddfbb03ed00fbe51213c393e88ab34849b0cce091b4de606ebd93</citedby><cites>FETCH-LOGICAL-c859t-91b8b6e7ba09ddfbb03ed00fbe51213c393e88ab34849b0cce091b4de606ebd93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19373939$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18033300$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>COLLISON, Lauren W</creatorcontrib><creatorcontrib>WORKMAN, Creg J</creatorcontrib><creatorcontrib>KUO, Timothy T</creatorcontrib><creatorcontrib>BOYD, Kelli</creatorcontrib><creatorcontrib>YAO WANG</creatorcontrib><creatorcontrib>VIGNALI, Kate M</creatorcontrib><creatorcontrib>CROSS, Richard</creatorcontrib><creatorcontrib>SEHY, David</creatorcontrib><creatorcontrib>BLUMBERG, Richard S</creatorcontrib><creatorcontrib>VIGNALI, Dario A. A</creatorcontrib><title>The inhibitory cytokine IL-35 contributes to regulatory T-cell function</title><title>Nature</title><addtitle>Nature</addtitle><description>Regulatory T (T(reg)) cells are a critical sub-population of CD4+ T cells that are essential for maintaining self tolerance and preventing autoimmunity, for limiting chronic inflammatory diseases, such as asthma and inflammatory bowel disease, and for regulating homeostatic lymphocyte expansion. However, they also suppress natural immune responses to parasites and viruses as well as anti-tumour immunity induced by therapeutic vaccines. Although the manipulation of T(reg) function is an important goal of immunotherapy, the molecules that mediate their suppressive activity remain largely unknown. Here we demonstrate that Epstein-Barr-virus-induced gene 3 (Ebi3, which encodes IL-27beta) and interleukin-12 alpha (Il12a, which encodes IL-12alpha/p35) are highly expressed by mouse Foxp3+ (forkhead box P3) T(reg) cells but not by resting or activated effector CD4+ T (T(eff)) cells, and that an Ebi3-IL-12alpha heterodimer is constitutively secreted by T(reg) but not T(eff) cells. Both Ebi3 and Il12a messenger RNA are markedly upregulated in T(reg) cells co-cultured with T(eff) cells, thereby boosting Ebi3 and IL-12alpha production in trans. T(reg)-cell restriction of this cytokine occurs because Ebi3 is a downstream target of Foxp3, a transcription factor that is required for T(reg)-cell development and function. Ebi3-/- and Il12a-/- T(reg) cells have significantly reduced regulatory activity in vitro and fail to control homeostatic proliferation and to cure inflammatory bowel disease in vivo. Because these phenotypic characteristics are distinct from those of other IL-12 family members, this novel Ebi3-IL-12alpha heterodimeric cytokine has been designated interleukin-35 (IL-35). Ectopic expression of IL-35 confers regulatory activity on naive T cells, whereas recombinant IL-35 suppresses T-cell proliferation. Taken together, these data identify IL-35 as a novel inhibitory cytokine that may be specifically produced by T(reg) cells and is required for maximal suppressive activity.</description><subject>Animals</subject><subject>Asthma</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell Proliferation</subject><subject>Cellular biology</subject><subject>Cytokines</subject><subject>Disease Models, Animal</subject><subject>Flow Cytometry</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genetics of the immune response</subject><subject>Humans</subject><subject>Immunobiology</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Inflammatory Bowel Diseases - metabolism</subject><subject>Interleukin-12 Subunit p35 - deficiency</subject><subject>Interleukin-12 Subunit p35 - genetics</subject><subject>Interleukin-12 Subunit p35 - metabolism</subject><subject>Lymphocytes</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Minor Histocompatibility Antigens</subject><subject>Molecular biology</subject><subject>Parasites</subject><subject>Receptors, Cytokine - deficiency</subject><subject>Receptors, Cytokine - genetics</subject><subject>Receptors, Cytokine - metabolism</subject><subject>T-Lymphocytes, Regulatory - cytology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>T-Lymphocytes, Regulatory - transplantation</subject><subject>Vaccines</subject><subject>Viruses</subject><issn>0028-0836</issn><issn>1476-4687</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0_GL0zAUB_AiijdPf_J3KYKKSM-Xpk2TH8fQczAUdOKPJUlfdzm7dJek4P57M2-wTe_c6A-F8nnfvjzykuQ5gQsClL-3MgwOgVFgD5IRKSqWFYxXD5MRQM4z4JSdJU-8vwaAklTF4-SMcKCUAoySy_kVpsZeGWVC79apXof-p7GYTmcZLVPd2-CMGgL6NPSpw8XQyT9wnmnsurQdrA6mt0-TR63sPD7bvs-T7x8_zCefstmXy-lkPMs0L0XIBFFcMayUBNE0rVJAsQFoFZYkJ1RTQZFzqWjBC6FAa4RYUjTIgKFqBD1P3tzmrlx_M6AP9dL4TSfSYj_4uipoCaLMN_L1fyXjJRVAqqOQsjyOixVHYU7idHlVHoVEcF5ygAhf_gWv-8HZOMA6h6JkNPYYUXaLFrLD2ti2D07qBVp0susttiZ-HhNBiyqe_mTPRWxWlNWuiQOvV-am3g-9H-0lXdyB4tPg0ug7Wz2tYO8Pbw8KNvcTf4WFHLyvp9--HoYftXu57-634_mPyefD5BP0v9na9d47bOuVM0vp1jWBerPB9d4GR_1ieyUGtcRmZ7crG8GrLZBey6510mrjd07QKm6RoL8BrBdFjg</recordid><startdate>20071122</startdate><enddate>20071122</enddate><creator>COLLISON, Lauren W</creator><creator>WORKMAN, Creg J</creator><creator>KUO, Timothy T</creator><creator>BOYD, Kelli</creator><creator>YAO WANG</creator><creator>VIGNALI, Kate M</creator><creator>CROSS, Richard</creator><creator>SEHY, David</creator><creator>BLUMBERG, Richard S</creator><creator>VIGNALI, Dario A. A</creator><general>Nature Publishing</general><general>Nature Publishing Group</general><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>ATWCN</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7SC</scope><scope>7SP</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope></search><sort><creationdate>20071122</creationdate><title>The inhibitory cytokine IL-35 contributes to regulatory T-cell function</title><author>COLLISON, Lauren W ; WORKMAN, Creg J ; KUO, Timothy T ; BOYD, Kelli ; YAO WANG ; VIGNALI, Kate M ; CROSS, Richard ; SEHY, David ; BLUMBERG, Richard S ; VIGNALI, Dario A. A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c859t-91b8b6e7ba09ddfbb03ed00fbe51213c393e88ab34849b0cce091b4de606ebd93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Asthma</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cell Proliferation</topic><topic>Cellular biology</topic><topic>Cytokines</topic><topic>Disease Models, Animal</topic><topic>Flow Cytometry</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Genetics of the immune response</topic><topic>Humans</topic><topic>Immunobiology</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Inflammatory Bowel Diseases - metabolism</topic><topic>Interleukin-12 Subunit p35 - deficiency</topic><topic>Interleukin-12 Subunit p35 - genetics</topic><topic>Interleukin-12 Subunit p35 - metabolism</topic><topic>Lymphocytes</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Minor Histocompatibility Antigens</topic><topic>Molecular biology</topic><topic>Parasites</topic><topic>Receptors, Cytokine - deficiency</topic><topic>Receptors, Cytokine - genetics</topic><topic>Receptors, Cytokine - metabolism</topic><topic>T-Lymphocytes, Regulatory - cytology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>T-Lymphocytes, Regulatory - transplantation</topic><topic>Vaccines</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>COLLISON, Lauren W</creatorcontrib><creatorcontrib>WORKMAN, Creg J</creatorcontrib><creatorcontrib>KUO, Timothy T</creatorcontrib><creatorcontrib>BOYD, Kelli</creatorcontrib><creatorcontrib>YAO WANG</creatorcontrib><creatorcontrib>VIGNALI, Kate M</creatorcontrib><creatorcontrib>CROSS, Richard</creatorcontrib><creatorcontrib>SEHY, David</creatorcontrib><creatorcontrib>BLUMBERG, Richard S</creatorcontrib><creatorcontrib>VIGNALI, Dario A. A</creatorcontrib><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>Gale In Context: Middle School</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Psychology Database (ProQuest)</collection><collection>ProQuest Research Library</collection><collection>ProQuest Science Journals</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials science collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>SIRS Editorial</collection><collection>Environment Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>MEDLINE - Academic</collection><jtitle>Nature</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>COLLISON, Lauren W</au><au>WORKMAN, Creg J</au><au>KUO, Timothy T</au><au>BOYD, Kelli</au><au>YAO WANG</au><au>VIGNALI, Kate M</au><au>CROSS, Richard</au><au>SEHY, David</au><au>BLUMBERG, Richard S</au><au>VIGNALI, Dario A. A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The inhibitory cytokine IL-35 contributes to regulatory T-cell function</atitle><jtitle>Nature</jtitle><addtitle>Nature</addtitle><date>2007-11-22</date><risdate>2007</risdate><volume>450</volume><issue>7169</issue><spage>566</spage><epage>569</epage><pages>566-569</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><eissn>1476-4679</eissn><coden>NATUAS</coden><abstract>Regulatory T (T(reg)) cells are a critical sub-population of CD4+ T cells that are essential for maintaining self tolerance and preventing autoimmunity, for limiting chronic inflammatory diseases, such as asthma and inflammatory bowel disease, and for regulating homeostatic lymphocyte expansion. However, they also suppress natural immune responses to parasites and viruses as well as anti-tumour immunity induced by therapeutic vaccines. Although the manipulation of T(reg) function is an important goal of immunotherapy, the molecules that mediate their suppressive activity remain largely unknown. Here we demonstrate that Epstein-Barr-virus-induced gene 3 (Ebi3, which encodes IL-27beta) and interleukin-12 alpha (Il12a, which encodes IL-12alpha/p35) are highly expressed by mouse Foxp3+ (forkhead box P3) T(reg) cells but not by resting or activated effector CD4+ T (T(eff)) cells, and that an Ebi3-IL-12alpha heterodimer is constitutively secreted by T(reg) but not T(eff) cells. Both Ebi3 and Il12a messenger RNA are markedly upregulated in T(reg) cells co-cultured with T(eff) cells, thereby boosting Ebi3 and IL-12alpha production in trans. T(reg)-cell restriction of this cytokine occurs because Ebi3 is a downstream target of Foxp3, a transcription factor that is required for T(reg)-cell development and function. Ebi3-/- and Il12a-/- T(reg) cells have significantly reduced regulatory activity in vitro and fail to control homeostatic proliferation and to cure inflammatory bowel disease in vivo. Because these phenotypic characteristics are distinct from those of other IL-12 family members, this novel Ebi3-IL-12alpha heterodimeric cytokine has been designated interleukin-35 (IL-35). Ectopic expression of IL-35 confers regulatory activity on naive T cells, whereas recombinant IL-35 suppresses T-cell proliferation. Taken together, these data identify IL-35 as a novel inhibitory cytokine that may be specifically produced by T(reg) cells and is required for maximal suppressive activity.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>18033300</pmid><doi>10.1038/nature06306</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature, 2007-11, Vol.450 (7169), p.566-569 |
| issn | 0028-0836 1476-4687 1476-4679 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743509529 |
| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | Animals Asthma Biological and medical sciences Cell Line Cell Proliferation Cellular biology Cytokines Disease Models, Animal Flow Cytometry Forkhead Transcription Factors - metabolism Fundamental and applied biological sciences. Psychology Fundamental immunology Gene expression Gene Expression Regulation Genetics of the immune response Humans Immunobiology Immunology Immunotherapy Inflammatory Bowel Diseases - metabolism Interleukin-12 Subunit p35 - deficiency Interleukin-12 Subunit p35 - genetics Interleukin-12 Subunit p35 - metabolism Lymphocytes Mice Mice, Inbred C57BL Minor Histocompatibility Antigens Molecular biology Parasites Receptors, Cytokine - deficiency Receptors, Cytokine - genetics Receptors, Cytokine - metabolism T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism T-Lymphocytes, Regulatory - transplantation Vaccines Viruses |
| title | The inhibitory cytokine IL-35 contributes to regulatory T-cell function |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T22%3A41%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20inhibitory%20cytokine%20IL-35%20contributes%20to%20regulatory%20T-cell%20function&rft.jtitle=Nature&rft.au=COLLISON,%20Lauren%20W&rft.date=2007-11-22&rft.volume=450&rft.issue=7169&rft.spage=566&rft.epage=569&rft.pages=566-569&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/nature06306&rft_dat=%3Cgale_proqu%3EA193477433%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=204563853&rft_id=info:pmid/18033300&rft_galeid=A193477433&rfr_iscdi=true |