The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates [T.sub.H]17 differentiation
Deregulation of the [T.sub.H]17 subset of helper T cells is closely linked with immunological disorders and inflammatory diseases. However, the mechanism by which [T.sub.H]17 cells are regulated remains elusive. Here we found that the phosphatase DUSP2 (PACI) negatively regulated the development of...
Gespeichert in:
| Veröffentlicht in: | Nature immunology 2015-12, p.1263 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | |
| container_start_page | 1263 |
| container_title | Nature immunology |
| container_volume | |
| creator | Lu, Dan Liu, Liang Ji, Xin Gao, Yanan Chen, Xi Liu, Yu Liu, Yang Zhao, Xuyang Li, Yan Li, Yunqiao Jin, Yan Zhang, Yu McNutt, Michael A Yin, Yuxin |
| description | Deregulation of the [T.sub.H]17 subset of helper T cells is closely linked with immunological disorders and inflammatory diseases. However, the mechanism by which [T.sub.H]17 cells are regulated remains elusive. Here we found that the phosphatase DUSP2 (PACI) negatively regulated the development of [T.sub.H]17 cells. DUSP2 was directly associated with the signal transducer and transcription activator STAT3 and attenuated its activity through dephosphorylation of STAT3 at Tyr705 and Ser727. DUSP2-deficient mice exhibited severe susceptibility to experimental colitis, with enhanced differentiation of [T.sub.H]17 cells and secretion of proinflammatory cytokines. In clinical patients with ulcerative colitis, DUSP2 was downregulated by DNA methylation and was not induced during T cell activation. Our data demonstrate that DUSP2 is a true STAT3 phosphatase that modulates the development of [T.sub.H]17 cells in the autoimmune response and inflammation. |
| doi_str_mv | 10.1038/ni.3278 |
| format | Article |
| fullrecord | <record><control><sourceid>gale</sourceid><recordid>TN_cdi_gale_infotracmisc_A435795390</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A435795390</galeid><sourcerecordid>A435795390</sourcerecordid><originalsourceid>FETCH-LOGICAL-g1010-a3e64034e9ecfb8ee8e848732cfd40e5ebfd1bd7426485b93bb2e9b5ed307f8d3</originalsourceid><addsrcrecordid>eNptUFtLwzAUDqLgnOJfCPjkQ2tubdPHMS8bDBTXPYmMpDnpIl07mkzUX2_nRBTkPJzLd4HzIXROSUwJl1eNiznL5AEa0ITlEctpevgzE3mMTrx_IYSKLBUD9FGsAG9Wrd-sVFAe8PVi_sBw2Taha2uPQw-rMrhXF95xa7_20KnGl53bBNc2e1SFtsPzYlRwrBqDO6i2tQrg8VMR-62OJ880w8ZZCx00wamd8hQdWVV7OPvuQ7S4vSnGk2h2fzcdj2ZRRQklkeKQCsIF5FBaLQEkSCEzzkprBIEEtDVUm0ywVMhE51xrBrlOwHCSWWn4EF3sfStVw9I1tu0fKNfOl8uR4EmWJzwnPSv-h9WXgbXr4wDr-vsfweUfwS4yeAuV2nq_nM4ff3M_ARcXfHg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates [T.sub.H]17 differentiation</title><source>Nature</source><source>Alma/SFX Local Collection</source><creator>Lu, Dan ; Liu, Liang ; Ji, Xin ; Gao, Yanan ; Chen, Xi ; Liu, Yu ; Liu, Yang ; Zhao, Xuyang ; Li, Yan ; Li, Yunqiao ; Jin, Yan ; Zhang, Yu ; McNutt, Michael A ; Yin, Yuxin</creator><creatorcontrib>Lu, Dan ; Liu, Liang ; Ji, Xin ; Gao, Yanan ; Chen, Xi ; Liu, Yu ; Liu, Yang ; Zhao, Xuyang ; Li, Yan ; Li, Yunqiao ; Jin, Yan ; Zhang, Yu ; McNutt, Michael A ; Yin, Yuxin</creatorcontrib><description>Deregulation of the [T.sub.H]17 subset of helper T cells is closely linked with immunological disorders and inflammatory diseases. However, the mechanism by which [T.sub.H]17 cells are regulated remains elusive. Here we found that the phosphatase DUSP2 (PACI) negatively regulated the development of [T.sub.H]17 cells. DUSP2 was directly associated with the signal transducer and transcription activator STAT3 and attenuated its activity through dephosphorylation of STAT3 at Tyr705 and Ser727. DUSP2-deficient mice exhibited severe susceptibility to experimental colitis, with enhanced differentiation of [T.sub.H]17 cells and secretion of proinflammatory cytokines. In clinical patients with ulcerative colitis, DUSP2 was downregulated by DNA methylation and was not induced during T cell activation. Our data demonstrate that DUSP2 is a true STAT3 phosphatase that modulates the development of [T.sub.H]17 cells in the autoimmune response and inflammation.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni.3278</identifier><language>eng</language><publisher>Nature Publishing Group</publisher><subject>Autoimmunity ; Care and treatment ; Development and progression ; Genetic aspects ; Genetic transcription ; Methylation ; Ulcerative colitis</subject><ispartof>Nature immunology, 2015-12, p.1263</ispartof><rights>COPYRIGHT 2015 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></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></links><search><creatorcontrib>Lu, Dan</creatorcontrib><creatorcontrib>Liu, Liang</creatorcontrib><creatorcontrib>Ji, Xin</creatorcontrib><creatorcontrib>Gao, Yanan</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Zhao, Xuyang</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Li, Yunqiao</creatorcontrib><creatorcontrib>Jin, Yan</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>McNutt, Michael A</creatorcontrib><creatorcontrib>Yin, Yuxin</creatorcontrib><title>The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates [T.sub.H]17 differentiation</title><title>Nature immunology</title><description>Deregulation of the [T.sub.H]17 subset of helper T cells is closely linked with immunological disorders and inflammatory diseases. However, the mechanism by which [T.sub.H]17 cells are regulated remains elusive. Here we found that the phosphatase DUSP2 (PACI) negatively regulated the development of [T.sub.H]17 cells. DUSP2 was directly associated with the signal transducer and transcription activator STAT3 and attenuated its activity through dephosphorylation of STAT3 at Tyr705 and Ser727. DUSP2-deficient mice exhibited severe susceptibility to experimental colitis, with enhanced differentiation of [T.sub.H]17 cells and secretion of proinflammatory cytokines. In clinical patients with ulcerative colitis, DUSP2 was downregulated by DNA methylation and was not induced during T cell activation. Our data demonstrate that DUSP2 is a true STAT3 phosphatase that modulates the development of [T.sub.H]17 cells in the autoimmune response and inflammation.</description><subject>Autoimmunity</subject><subject>Care and treatment</subject><subject>Development and progression</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Methylation</subject><subject>Ulcerative colitis</subject><issn>1529-2908</issn><issn>1529-2916</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNptUFtLwzAUDqLgnOJfCPjkQ2tubdPHMS8bDBTXPYmMpDnpIl07mkzUX2_nRBTkPJzLd4HzIXROSUwJl1eNiznL5AEa0ITlEctpevgzE3mMTrx_IYSKLBUD9FGsAG9Wrd-sVFAe8PVi_sBw2Taha2uPQw-rMrhXF95xa7_20KnGl53bBNc2e1SFtsPzYlRwrBqDO6i2tQrg8VMR-62OJ880w8ZZCx00wamd8hQdWVV7OPvuQ7S4vSnGk2h2fzcdj2ZRRQklkeKQCsIF5FBaLQEkSCEzzkprBIEEtDVUm0ywVMhE51xrBrlOwHCSWWn4EF3sfStVw9I1tu0fKNfOl8uR4EmWJzwnPSv-h9WXgbXr4wDr-vsfweUfwS4yeAuV2nq_nM4ff3M_ARcXfHg</recordid><startdate>20151201</startdate><enddate>20151201</enddate><creator>Lu, Dan</creator><creator>Liu, Liang</creator><creator>Ji, Xin</creator><creator>Gao, Yanan</creator><creator>Chen, Xi</creator><creator>Liu, Yu</creator><creator>Liu, Yang</creator><creator>Zhao, Xuyang</creator><creator>Li, Yan</creator><creator>Li, Yunqiao</creator><creator>Jin, Yan</creator><creator>Zhang, Yu</creator><creator>McNutt, Michael A</creator><creator>Yin, Yuxin</creator><general>Nature Publishing Group</general><scope>ISR</scope></search><sort><creationdate>20151201</creationdate><title>The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates [T.sub.H]17 differentiation</title><author>Lu, Dan ; Liu, Liang ; Ji, Xin ; Gao, Yanan ; Chen, Xi ; Liu, Yu ; Liu, Yang ; Zhao, Xuyang ; Li, Yan ; Li, Yunqiao ; Jin, Yan ; Zhang, Yu ; McNutt, Michael A ; Yin, Yuxin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g1010-a3e64034e9ecfb8ee8e848732cfd40e5ebfd1bd7426485b93bb2e9b5ed307f8d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Autoimmunity</topic><topic>Care and treatment</topic><topic>Development and progression</topic><topic>Genetic aspects</topic><topic>Genetic transcription</topic><topic>Methylation</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Dan</creatorcontrib><creatorcontrib>Liu, Liang</creatorcontrib><creatorcontrib>Ji, Xin</creatorcontrib><creatorcontrib>Gao, Yanan</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Zhao, Xuyang</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Li, Yunqiao</creatorcontrib><creatorcontrib>Jin, Yan</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>McNutt, Michael A</creatorcontrib><creatorcontrib>Yin, Yuxin</creatorcontrib><collection>Gale In Context: Science</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Dan</au><au>Liu, Liang</au><au>Ji, Xin</au><au>Gao, Yanan</au><au>Chen, Xi</au><au>Liu, Yu</au><au>Liu, Yang</au><au>Zhao, Xuyang</au><au>Li, Yan</au><au>Li, Yunqiao</au><au>Jin, Yan</au><au>Zhang, Yu</au><au>McNutt, Michael A</au><au>Yin, Yuxin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates [T.sub.H]17 differentiation</atitle><jtitle>Nature immunology</jtitle><date>2015-12-01</date><risdate>2015</risdate><spage>1263</spage><pages>1263-</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>Deregulation of the [T.sub.H]17 subset of helper T cells is closely linked with immunological disorders and inflammatory diseases. However, the mechanism by which [T.sub.H]17 cells are regulated remains elusive. Here we found that the phosphatase DUSP2 (PACI) negatively regulated the development of [T.sub.H]17 cells. DUSP2 was directly associated with the signal transducer and transcription activator STAT3 and attenuated its activity through dephosphorylation of STAT3 at Tyr705 and Ser727. DUSP2-deficient mice exhibited severe susceptibility to experimental colitis, with enhanced differentiation of [T.sub.H]17 cells and secretion of proinflammatory cytokines. In clinical patients with ulcerative colitis, DUSP2 was downregulated by DNA methylation and was not induced during T cell activation. Our data demonstrate that DUSP2 is a true STAT3 phosphatase that modulates the development of [T.sub.H]17 cells in the autoimmune response and inflammation.</abstract><pub>Nature Publishing Group</pub><doi>10.1038/ni.3278</doi><tpages>14</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1529-2908 |
| ispartof | Nature immunology, 2015-12, p.1263 |
| issn | 1529-2908 1529-2916 |
| language | eng |
| recordid | cdi_gale_infotracmisc_A435795390 |
| source | Nature; Alma/SFX Local Collection |
| subjects | Autoimmunity Care and treatment Development and progression Genetic aspects Genetic transcription Methylation Ulcerative colitis |
| title | The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates [T.sub.H]17 differentiation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-14T18%3A54%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20phosphatase%20DUSP2%20controls%20the%20activity%20of%20the%20transcription%20activator%20STAT3%20and%20regulates%20%5BT.sub.H%5D17%20differentiation&rft.jtitle=Nature%20immunology&rft.au=Lu,%20Dan&rft.date=2015-12-01&rft.spage=1263&rft.pages=1263-&rft.issn=1529-2908&rft.eissn=1529-2916&rft_id=info:doi/10.1038/ni.3278&rft_dat=%3Cgale%3EA435795390%3C/gale%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rft_galeid=A435795390&rfr_iscdi=true |