Ikaros integrates endocrine and immune system development
Ikaros transcription factors are essential regulators of lymphopoiesis and the development of the immune system. We now show that Ikaros is expressed in hormone-producing pituitary corticomelanotroph cells, where it binds the proopiomelanocortin promoter and regulates endogenous gene expression. Los...
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| Veröffentlicht in: | The Journal of clinical investigation 2005-04, Vol.115 (4), p.1021-1029 |
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| creator | Ezzat, Shereen Mader, Rene Yu, ShunJiang Ning, Terry Poussier, Philippe Asa, Sylvia L |
| description | Ikaros transcription factors are essential regulators of lymphopoiesis and the development of the immune system. We now show that Ikaros is expressed in hormone-producing pituitary corticomelanotroph cells, where it binds the proopiomelanocortin promoter and regulates endogenous gene expression. Loss of Ikaros in vivo results in contraction of the pituitary corticomelanotroph population, reduced circulating adrenocorticotrophic hormone levels, and adrenal glucocorticoid insufficiency. While hemopoietic reconstitution failed to correct this hormonal deficit, the phenotype of reduced body weight and diminished survival was rescued by systemic glucocorticoid-hormone administration. Given the established immunomodulatory properties of glucocorticoid hormones, these findings reveal a novel role for Ikaros in orchestrating immune-endocrine development and function. |
| doi_str_mv | 10.1172/JCI200522486 |
| format | Article |
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We now show that Ikaros is expressed in hormone-producing pituitary corticomelanotroph cells, where it binds the proopiomelanocortin promoter and regulates endogenous gene expression. Loss of Ikaros in vivo results in contraction of the pituitary corticomelanotroph population, reduced circulating adrenocorticotrophic hormone levels, and adrenal glucocorticoid insufficiency. While hemopoietic reconstitution failed to correct this hormonal deficit, the phenotype of reduced body weight and diminished survival was rescued by systemic glucocorticoid-hormone administration. Given the established immunomodulatory properties of glucocorticoid hormones, these findings reveal a novel role for Ikaros in orchestrating immune-endocrine development and function.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI200522486</identifier><identifier>PMID: 15841184</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Adrenocorticotropic Hormone - genetics ; Adrenocorticotropic Hormone - metabolism ; Animals ; Antibodies ; Base Sequence ; Binding Sites ; Biomedical research ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cells, Cultured ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Endocrine System - growth & development ; Endocrine System - metabolism ; Fibroblasts ; Gene expression ; Gene Expression Regulation ; Growth factors ; Humans ; Hypothalamo-Hypophyseal System - physiology ; Ikaros Transcription Factor ; Immune system ; Immune System - growth & development ; Immune System - metabolism ; Lymphocytes ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Pituitary Gland - cytology ; Pituitary Gland - metabolism ; Pituitary-Adrenal System - physiology ; Pro-Opiomelanocortin - genetics ; Pro-Opiomelanocortin - metabolism ; Promoter Regions, Genetic ; Proteins ; Survival Rate ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>The Journal of clinical investigation, 2005-04, Vol.115 (4), p.1021-1029</ispartof><rights>Copyright American Society for Clinical Investigation Apr 2005</rights><rights>Copyright © 2005, American Society for Clinical Investigation 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-fe9837152ed6f6621e40fbfaee7f68c0c45e20cef16c3be1a7cdeb0100526213</citedby><cites>FETCH-LOGICAL-c409t-fe9837152ed6f6621e40fbfaee7f68c0c45e20cef16c3be1a7cdeb0100526213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1070405/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1070405/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15841184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ezzat, Shereen</creatorcontrib><creatorcontrib>Mader, Rene</creatorcontrib><creatorcontrib>Yu, ShunJiang</creatorcontrib><creatorcontrib>Ning, Terry</creatorcontrib><creatorcontrib>Poussier, Philippe</creatorcontrib><creatorcontrib>Asa, Sylvia L</creatorcontrib><title>Ikaros integrates endocrine and immune system development</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Ikaros transcription factors are essential regulators of lymphopoiesis and the development of the immune system. We now show that Ikaros is expressed in hormone-producing pituitary corticomelanotroph cells, where it binds the proopiomelanocortin promoter and regulates endogenous gene expression. Loss of Ikaros in vivo results in contraction of the pituitary corticomelanotroph population, reduced circulating adrenocorticotrophic hormone levels, and adrenal glucocorticoid insufficiency. While hemopoietic reconstitution failed to correct this hormonal deficit, the phenotype of reduced body weight and diminished survival was rescued by systemic glucocorticoid-hormone administration. Given the established immunomodulatory properties of glucocorticoid hormones, these findings reveal a novel role for Ikaros in orchestrating immune-endocrine development and function.</description><subject>Adrenocorticotropic Hormone - genetics</subject><subject>Adrenocorticotropic Hormone - metabolism</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Base Sequence</subject><subject>Binding Sites</subject><subject>Biomedical research</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cells, Cultured</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endocrine System - growth & development</subject><subject>Endocrine System - metabolism</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Hypothalamo-Hypophyseal System - physiology</subject><subject>Ikaros Transcription Factor</subject><subject>Immune system</subject><subject>Immune System - growth & development</subject><subject>Immune System - metabolism</subject><subject>Lymphocytes</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Molecular Sequence Data</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Pituitary Gland - cytology</subject><subject>Pituitary Gland - metabolism</subject><subject>Pituitary-Adrenal System - physiology</subject><subject>Pro-Opiomelanocortin - genetics</subject><subject>Pro-Opiomelanocortin - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>Survival Rate</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkctPwzAMxiMEgvG4cUYVB04U7DRpswsSmngMIXHhHqWpOzr6GEk7af89gU0wONmSf_rszx9jpwhXiBm_fppMOYDkXKh0h41QShUrnqhdNgLgGI-zRB2wQ-_nACiEFPvsAKUSiEqM2Hj6blzno6rtaeZMTz6ituisq1qKTFtEVdMMofUr31MTFbSkuls01PbHbK80taeTTT1ir_d3r5PH-PnlYTq5fY6tgHEflzRWSYaSU5GWacqRBJR5aYiyMlUWrJDEwVKJqU1yQpPZgnLAL0uBTo7YzVp2MeQNFTZsdqbWC1c1xq10Zyr9d9JWb3rWLTVCBgJkELjYCLjuYyDf66byluratNQNXqdZJqXEJIDn_8B5N7g2eNPfD5YK0gBdriEbvuYdlT-XIOivPPR2HgE_277-F94EkHwCIyWGWA</recordid><startdate>200504</startdate><enddate>200504</enddate><creator>Ezzat, Shereen</creator><creator>Mader, Rene</creator><creator>Yu, ShunJiang</creator><creator>Ning, Terry</creator><creator>Poussier, Philippe</creator><creator>Asa, Sylvia L</creator><general>American Society for Clinical Investigation</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200504</creationdate><title>Ikaros integrates endocrine and immune system development</title><author>Ezzat, Shereen ; Mader, Rene ; Yu, ShunJiang ; Ning, Terry ; Poussier, Philippe ; Asa, Sylvia L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-fe9837152ed6f6621e40fbfaee7f68c0c45e20cef16c3be1a7cdeb0100526213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adrenocorticotropic Hormone - genetics</topic><topic>Adrenocorticotropic Hormone - metabolism</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Base Sequence</topic><topic>Binding Sites</topic><topic>Biomedical research</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cells, Cultured</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Endocrine System - growth & development</topic><topic>Endocrine System - metabolism</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Hypothalamo-Hypophyseal System - physiology</topic><topic>Ikaros Transcription Factor</topic><topic>Immune system</topic><topic>Immune System - growth & development</topic><topic>Immune System - metabolism</topic><topic>Lymphocytes</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Molecular Sequence Data</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Pituitary Gland - cytology</topic><topic>Pituitary Gland - metabolism</topic><topic>Pituitary-Adrenal System - physiology</topic><topic>Pro-Opiomelanocortin - genetics</topic><topic>Pro-Opiomelanocortin - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins</topic><topic>Survival Rate</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ezzat, Shereen</creatorcontrib><creatorcontrib>Mader, Rene</creatorcontrib><creatorcontrib>Yu, ShunJiang</creatorcontrib><creatorcontrib>Ning, Terry</creatorcontrib><creatorcontrib>Poussier, Philippe</creatorcontrib><creatorcontrib>Asa, Sylvia L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>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>ProQuest Pharma Collection</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ezzat, Shereen</au><au>Mader, Rene</au><au>Yu, ShunJiang</au><au>Ning, Terry</au><au>Poussier, Philippe</au><au>Asa, Sylvia L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ikaros integrates endocrine and immune system development</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2005-04</date><risdate>2005</risdate><volume>115</volume><issue>4</issue><spage>1021</spage><epage>1029</epage><pages>1021-1029</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>Ikaros transcription factors are essential regulators of lymphopoiesis and the development of the immune system. We now show that Ikaros is expressed in hormone-producing pituitary corticomelanotroph cells, where it binds the proopiomelanocortin promoter and regulates endogenous gene expression. Loss of Ikaros in vivo results in contraction of the pituitary corticomelanotroph population, reduced circulating adrenocorticotrophic hormone levels, and adrenal glucocorticoid insufficiency. While hemopoietic reconstitution failed to correct this hormonal deficit, the phenotype of reduced body weight and diminished survival was rescued by systemic glucocorticoid-hormone administration. Given the established immunomodulatory properties of glucocorticoid hormones, these findings reveal a novel role for Ikaros in orchestrating immune-endocrine development and function.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>15841184</pmid><doi>10.1172/JCI200522486</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Adrenocorticotropic Hormone - genetics Adrenocorticotropic Hormone - metabolism Animals Antibodies Base Sequence Binding Sites Biomedical research Carrier Proteins - genetics Carrier Proteins - metabolism Cells, Cultured DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Endocrine System - growth & development Endocrine System - metabolism Fibroblasts Gene expression Gene Expression Regulation Growth factors Humans Hypothalamo-Hypophyseal System - physiology Ikaros Transcription Factor Immune system Immune System - growth & development Immune System - metabolism Lymphocytes Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Pituitary Gland - cytology Pituitary Gland - metabolism Pituitary-Adrenal System - physiology Pro-Opiomelanocortin - genetics Pro-Opiomelanocortin - metabolism Promoter Regions, Genetic Proteins Survival Rate Transcription Factors - genetics Transcription Factors - metabolism |
| title | Ikaros integrates endocrine and immune system development |
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