Bidirectional immunoregulation of calcineurin inhibitor tacrolimus on FOXP3 transcription?
Summary The imbalance between regulatory T cells (Treg) and effector T cells is important for maintaining of psoriasis vulgaris. FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatme...
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| Veröffentlicht in: | Medical hypotheses 2011-02, Vol.76 (2), p.178-180 |
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| creator | Shen, Zhu Song, Qiuhe Chen, Ling Zhong, Baiyu Tang, Shuqian Hao, Fei |
| description | Summary The imbalance between regulatory T cells (Treg) and effector T cells is important for maintaining of psoriasis vulgaris. FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatment of psoriasis vulgaris. Data show that tacrolimus has multiple impacts on FOXP3, but the exact pharmacological mechanism of tacrolimus on FOXP3 have yet to be elucidated. We herein suggest the bidirectional immunoregulation of tacrolimus on FOXP3. High concentration of tacrolimus renders the cooperation of NFAT with STAT6 and NF-κB to activate GATA3 transcription. On the contrary, low concentration of tacrolimus results in higher nucleus level of NFAT, which directly binds to FOXP3 enhancer and/or cooperates with Smad3 to activate FOXP3 transcription. Further studies using loss of function and over-expression methods are needed to determine the detailed molecules involved in this bidirectional immunoregulation of tacrolimus on FOXP3. |
| doi_str_mv | 10.1016/j.mehy.2010.09.011 |
| format | Article |
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FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatment of psoriasis vulgaris. Data show that tacrolimus has multiple impacts on FOXP3, but the exact pharmacological mechanism of tacrolimus on FOXP3 have yet to be elucidated. We herein suggest the bidirectional immunoregulation of tacrolimus on FOXP3. High concentration of tacrolimus renders the cooperation of NFAT with STAT6 and NF-κB to activate GATA3 transcription. On the contrary, low concentration of tacrolimus results in higher nucleus level of NFAT, which directly binds to FOXP3 enhancer and/or cooperates with Smad3 to activate FOXP3 transcription. Further studies using loss of function and over-expression methods are needed to determine the detailed molecules involved in this bidirectional immunoregulation of tacrolimus on FOXP3.</description><identifier>ISSN: 0306-9877</identifier><identifier>EISSN: 1532-2777</identifier><identifier>DOI: 10.1016/j.mehy.2010.09.011</identifier><identifier>PMID: 20937549</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Animals ; Calcineurin Inhibitors ; Cell Nucleus - metabolism ; Dose-Response Relationship, Drug ; Forkhead Transcription Factors - metabolism ; GATA3 Transcription Factor - metabolism ; Gene Expression Regulation ; Humans ; Immunosuppressive Agents - pharmacology ; Internal Medicine ; NFATC Transcription Factors - metabolism ; Psoriasis - metabolism ; STAT6 Transcription Factor - metabolism ; T-Lymphocytes, Regulatory - metabolism ; Tacrolimus - pharmacology ; Transcription Factors - metabolism</subject><ispartof>Medical hypotheses, 2011-02, Vol.76 (2), p.178-180</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>Copyright © 2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c476t-5deae205f983dff6162f2e985961f9fe30b3808b3aaca626aec094d7ab2ad4bb3</citedby><cites>FETCH-LOGICAL-c476t-5deae205f983dff6162f2e985961f9fe30b3808b3aaca626aec094d7ab2ad4bb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mehy.2010.09.011$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20937549$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shen, Zhu</creatorcontrib><creatorcontrib>Song, Qiuhe</creatorcontrib><creatorcontrib>Chen, Ling</creatorcontrib><creatorcontrib>Zhong, Baiyu</creatorcontrib><creatorcontrib>Tang, Shuqian</creatorcontrib><creatorcontrib>Hao, Fei</creatorcontrib><title>Bidirectional immunoregulation of calcineurin inhibitor tacrolimus on FOXP3 transcription?</title><title>Medical hypotheses</title><addtitle>Med Hypotheses</addtitle><description>Summary The imbalance between regulatory T cells (Treg) and effector T cells is important for maintaining of psoriasis vulgaris. FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatment of psoriasis vulgaris. Data show that tacrolimus has multiple impacts on FOXP3, but the exact pharmacological mechanism of tacrolimus on FOXP3 have yet to be elucidated. We herein suggest the bidirectional immunoregulation of tacrolimus on FOXP3. High concentration of tacrolimus renders the cooperation of NFAT with STAT6 and NF-κB to activate GATA3 transcription. On the contrary, low concentration of tacrolimus results in higher nucleus level of NFAT, which directly binds to FOXP3 enhancer and/or cooperates with Smad3 to activate FOXP3 transcription. Further studies using loss of function and over-expression methods are needed to determine the detailed molecules involved in this bidirectional immunoregulation of tacrolimus on FOXP3.</description><subject>Animals</subject><subject>Calcineurin Inhibitors</subject><subject>Cell Nucleus - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>GATA3 Transcription Factor - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Internal Medicine</subject><subject>NFATC Transcription Factors - metabolism</subject><subject>Psoriasis - metabolism</subject><subject>STAT6 Transcription Factor - metabolism</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>Tacrolimus - pharmacology</subject><subject>Transcription Factors - metabolism</subject><issn>0306-9877</issn><issn>1532-2777</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9rFTEUxYNY7LP6BVzI7FzNM39mkgmIosWqUGihCuImZDI39j5nktdkRnjf3gyvunDRVeByziHndwh5weiWUSZf77YT3B62nJYD1VvK2COyYa3gNVdKPSYbKqisdafUKXma845SqhvRPSGnnGqh2kZvyI8POGACN2MMdqxwmpYQE_xcRruequgrZ0eHAZaEocJwiz3OMVWzdSmOOC25KrKLq-_XopqTDdkl3K_Wd8_Iibdjhuf37xn5dvHx6_nn-vLq05fz95e1a5Sc63YAC5y2Xndi8F4yyT0H3bVaMq89CNqLjna9sNZZyaUFV2oMyvbcDk3fizPy6pi7T_FugTybCbODcbQB4pJNJ1RTunJVlPyoLF_POYE3-4STTQfDqFmRmp1ZkZoVqaHaFKTF9PI-fuknGP5Z_jIsgjdHAZSSvxGSyQ4hODiCNUPEh_Pf_md3IwYs1H_BAfIuLqkskw0zmRtqbtZR101ZmVPIthN_AGn0nvE</recordid><startdate>20110201</startdate><enddate>20110201</enddate><creator>Shen, Zhu</creator><creator>Song, Qiuhe</creator><creator>Chen, Ling</creator><creator>Zhong, Baiyu</creator><creator>Tang, Shuqian</creator><creator>Hao, Fei</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>20110201</creationdate><title>Bidirectional immunoregulation of calcineurin inhibitor tacrolimus on FOXP3 transcription?</title><author>Shen, Zhu ; Song, Qiuhe ; Chen, Ling ; Zhong, Baiyu ; Tang, Shuqian ; Hao, Fei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c476t-5deae205f983dff6162f2e985961f9fe30b3808b3aaca626aec094d7ab2ad4bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Calcineurin Inhibitors</topic><topic>Cell Nucleus - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>GATA3 Transcription Factor - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Internal Medicine</topic><topic>NFATC Transcription Factors - metabolism</topic><topic>Psoriasis - metabolism</topic><topic>STAT6 Transcription Factor - metabolism</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>Tacrolimus - pharmacology</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shen, Zhu</creatorcontrib><creatorcontrib>Song, Qiuhe</creatorcontrib><creatorcontrib>Chen, Ling</creatorcontrib><creatorcontrib>Zhong, Baiyu</creatorcontrib><creatorcontrib>Tang, Shuqian</creatorcontrib><creatorcontrib>Hao, Fei</creatorcontrib><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><jtitle>Medical hypotheses</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shen, Zhu</au><au>Song, Qiuhe</au><au>Chen, Ling</au><au>Zhong, Baiyu</au><au>Tang, Shuqian</au><au>Hao, Fei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bidirectional immunoregulation of calcineurin inhibitor tacrolimus on FOXP3 transcription?</atitle><jtitle>Medical hypotheses</jtitle><addtitle>Med Hypotheses</addtitle><date>2011-02-01</date><risdate>2011</risdate><volume>76</volume><issue>2</issue><spage>178</spage><epage>180</epage><pages>178-180</pages><issn>0306-9877</issn><eissn>1532-2777</eissn><abstract>Summary The imbalance between regulatory T cells (Treg) and effector T cells is important for maintaining of psoriasis vulgaris. FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatment of psoriasis vulgaris. Data show that tacrolimus has multiple impacts on FOXP3, but the exact pharmacological mechanism of tacrolimus on FOXP3 have yet to be elucidated. We herein suggest the bidirectional immunoregulation of tacrolimus on FOXP3. High concentration of tacrolimus renders the cooperation of NFAT with STAT6 and NF-κB to activate GATA3 transcription. On the contrary, low concentration of tacrolimus results in higher nucleus level of NFAT, which directly binds to FOXP3 enhancer and/or cooperates with Smad3 to activate FOXP3 transcription. Further studies using loss of function and over-expression methods are needed to determine the detailed molecules involved in this bidirectional immunoregulation of tacrolimus on FOXP3.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>20937549</pmid><doi>10.1016/j.mehy.2010.09.011</doi><tpages>3</tpages></addata></record> |
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| subjects | Animals Calcineurin Inhibitors Cell Nucleus - metabolism Dose-Response Relationship, Drug Forkhead Transcription Factors - metabolism GATA3 Transcription Factor - metabolism Gene Expression Regulation Humans Immunosuppressive Agents - pharmacology Internal Medicine NFATC Transcription Factors - metabolism Psoriasis - metabolism STAT6 Transcription Factor - metabolism T-Lymphocytes, Regulatory - metabolism Tacrolimus - pharmacology Transcription Factors - metabolism |
| title | Bidirectional immunoregulation of calcineurin inhibitor tacrolimus on FOXP3 transcription? |
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