CD4+CD25+ regulatory T cells attenuate cisplatin-induced nephrotoxicity in mice
Nephrotoxicity limits the use of cisplatin, a widely used chemotherapeutic agent for treatment of various malignancies. Overall, CD4+ T cells mediate cisplatin-induced renal injury; however, the CD4+CD25+ regulatory T-cell subset (CD4+CD25+ Treg) has broad suppressive effects on many different cell...
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| Veröffentlicht in: | Kidney international 2010-12, Vol.78 (11), p.1100-1109 |
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| creator | Lee, Hyojung Nho, Dukhee Chung, Hwan-Suck Lee, Heekyung Shin, Min-Kyu Kim, Sung-Hoon Bae, Hyunsu |
| description | Nephrotoxicity limits the use of cisplatin, a widely used chemotherapeutic agent for treatment of various malignancies. Overall, CD4+ T cells mediate cisplatin-induced renal injury; however, the CD4+CD25+ regulatory T-cell subset (CD4+CD25+ Treg) has broad suppressive effects on many different cell types. In this study, we determined whether CD4+CD25+ Treg cells had protective effects against cisplatin-induced acute renal injury in nu/nu mice that lack mature T cells. In these mice, there was marked attenuation of the decreased survival, renal dysfunction and tubular injury, renal tumor necrosis factor-α, and interleukin-1β cytokine levels. Furthermore, renal macrophage accumulation was reduced in CD4+CD25+ Treg cell-adoptive transferred nu/nu mice compared with control mice. Infusion of CD4+CD25+Treg cells into wild-type Balb/c mice reduced serum blood urea nitrogen and creatinine levels equivalent to those in nu/nu mice and extended their survival time after cisplatin injection. In contrast, depletion of CD4+CD25+ Treg cells in wild-type mice exacerbated kidney injury after cisplatin administration. Transcription factor Foxp3-positive cells (Treg cells) were detected in the kidneys of nu/nu mice after cisplatin injection. Our results suggest that CD4+CD25+ Treg cells directly affect cisplatin nephrotoxicity and their modulation represents an additional treatment strategy. |
| doi_str_mv | 10.1038/ki.2010.139 |
| format | Article |
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Overall, CD4+ T cells mediate cisplatin-induced renal injury; however, the CD4+CD25+ regulatory T-cell subset (CD4+CD25+ Treg) has broad suppressive effects on many different cell types. In this study, we determined whether CD4+CD25+ Treg cells had protective effects against cisplatin-induced acute renal injury in nu/nu mice that lack mature T cells. In these mice, there was marked attenuation of the decreased survival, renal dysfunction and tubular injury, renal tumor necrosis factor-α, and interleukin-1β cytokine levels. Furthermore, renal macrophage accumulation was reduced in CD4+CD25+ Treg cell-adoptive transferred nu/nu mice compared with control mice. Infusion of CD4+CD25+Treg cells into wild-type Balb/c mice reduced serum blood urea nitrogen and creatinine levels equivalent to those in nu/nu mice and extended their survival time after cisplatin injection. In contrast, depletion of CD4+CD25+ Treg cells in wild-type mice exacerbated kidney injury after cisplatin administration. Transcription factor Foxp3-positive cells (Treg cells) were detected in the kidneys of nu/nu mice after cisplatin injection. Our results suggest that CD4+CD25+ Treg cells directly affect cisplatin nephrotoxicity and their modulation represents an additional treatment strategy.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1038/ki.2010.139</identifier><identifier>PMID: 20463654</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>Basingstoke: Elsevier Inc</publisher><subject>Adoptive Transfer ; Animals ; Biological and medical sciences ; Biomarkers - blood ; Blood Urea Nitrogen ; Chemotaxis, Leukocyte ; Cisplatin ; Creatinine - blood ; Disease Models, Animal ; Forkhead Transcription Factors - metabolism ; Immunity, Innate ; Inflammation Mediators - metabolism ; Interleukin-1beta - metabolism ; Interleukin-2 Receptor alpha Subunit - analysis ; Kidney - immunology ; Kidney - metabolism ; Kidney - pathology ; Kidney Diseases - blood ; Kidney Diseases - chemically induced ; Kidney Diseases - immunology ; Kidney Diseases - pathology ; Kidney Diseases - prevention & control ; Macrophages - immunology ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nephrology. Urinary tract diseases ; nephrotoxicity ; regulatory T cell ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - transplantation ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - transplantation ; Time Factors ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Kidney international, 2010-12, Vol.78 (11), p.1100-1109</ispartof><rights>2010 International Society of Nephrology</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-564e380da390a033c99187e6102c11854965f2507ccf212a1ea69261c6197e0e3</citedby><cites>FETCH-LOGICAL-c428t-564e380da390a033c99187e6102c11854965f2507ccf212a1ea69261c6197e0e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/807800530?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,64364,64368,72218</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23448486$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20463654$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Hyojung</creatorcontrib><creatorcontrib>Nho, Dukhee</creatorcontrib><creatorcontrib>Chung, Hwan-Suck</creatorcontrib><creatorcontrib>Lee, Heekyung</creatorcontrib><creatorcontrib>Shin, Min-Kyu</creatorcontrib><creatorcontrib>Kim, Sung-Hoon</creatorcontrib><creatorcontrib>Bae, Hyunsu</creatorcontrib><title>CD4+CD25+ regulatory T cells attenuate cisplatin-induced nephrotoxicity in mice</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Nephrotoxicity limits the use of cisplatin, a widely used chemotherapeutic agent for treatment of various malignancies. Overall, CD4+ T cells mediate cisplatin-induced renal injury; however, the CD4+CD25+ regulatory T-cell subset (CD4+CD25+ Treg) has broad suppressive effects on many different cell types. In this study, we determined whether CD4+CD25+ Treg cells had protective effects against cisplatin-induced acute renal injury in nu/nu mice that lack mature T cells. In these mice, there was marked attenuation of the decreased survival, renal dysfunction and tubular injury, renal tumor necrosis factor-α, and interleukin-1β cytokine levels. Furthermore, renal macrophage accumulation was reduced in CD4+CD25+ Treg cell-adoptive transferred nu/nu mice compared with control mice. Infusion of CD4+CD25+Treg cells into wild-type Balb/c mice reduced serum blood urea nitrogen and creatinine levels equivalent to those in nu/nu mice and extended their survival time after cisplatin injection. In contrast, depletion of CD4+CD25+ Treg cells in wild-type mice exacerbated kidney injury after cisplatin administration. Transcription factor Foxp3-positive cells (Treg cells) were detected in the kidneys of nu/nu mice after cisplatin injection. Our results suggest that CD4+CD25+ Treg cells directly affect cisplatin nephrotoxicity and their modulation represents an additional treatment strategy.</description><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Blood Urea Nitrogen</subject><subject>Chemotaxis, Leukocyte</subject><subject>Cisplatin</subject><subject>Creatinine - blood</subject><subject>Disease Models, Animal</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Immunity, Innate</subject><subject>Inflammation Mediators - metabolism</subject><subject>Interleukin-1beta - metabolism</subject><subject>Interleukin-2 Receptor alpha Subunit - analysis</subject><subject>Kidney - immunology</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidney Diseases - blood</subject><subject>Kidney Diseases - chemically induced</subject><subject>Kidney Diseases - immunology</subject><subject>Kidney Diseases - pathology</subject><subject>Kidney Diseases - prevention & control</subject><subject>Macrophages - immunology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Nephrology. Urinary tract diseases</subject><subject>nephrotoxicity</subject><subject>regulatory T cell</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - transplantation</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - transplantation</subject><subject>Time Factors</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpt0M9r2zAUwHExVta022n3YgY9BbdPPy0fS9JfEMglOwtNft6UOHYqyWP576uQrL30JB768CS-hHyncEOB69uNv2FwGHj9iUyoZLyklZSfyQRAy5JJrs_JRYxryHPN4Qs5ZyAUV1JMyHI2F9PZnMlpEfD32Nk0hH2xKhx2XSxsStiPNmHhfNzlS9-Xvm9Gh03R4-5PGNLwzzuf9oXvi613-JWctbaL-O10XpKfD_er2VO5WD4-z-4WpRNMp1IqgVxDY3kNFjh3dU11hYoCc5RqKWolWyahcq5llFmKVtVMUadoXSEgvyQ_jnt3YXgZMSazHsbQ5yeNhkoDSA4ZTY_IhSHGgK3ZBb-1YW8omEM7s_Hm0M7kdllfnVaOv7bYvNn_sTK4PgEbne3aYPuc5d1xIbTQKjt5dJgD_PUYTHQe-xzNB3TJNIP_8AOvnD6Fyg</recordid><startdate>20101201</startdate><enddate>20101201</enddate><creator>Lee, Hyojung</creator><creator>Nho, Dukhee</creator><creator>Chung, Hwan-Suck</creator><creator>Lee, Heekyung</creator><creator>Shin, Min-Kyu</creator><creator>Kim, Sung-Hoon</creator><creator>Bae, Hyunsu</creator><general>Elsevier Inc</general><general>Nature Publishing Group</general><general>Elsevier Limited</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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20101201</creationdate><title>CD4+CD25+ regulatory T cells attenuate cisplatin-induced nephrotoxicity in mice</title><author>Lee, Hyojung ; Nho, Dukhee ; Chung, Hwan-Suck ; Lee, Heekyung ; Shin, Min-Kyu ; Kim, Sung-Hoon ; Bae, Hyunsu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-564e380da390a033c99187e6102c11854965f2507ccf212a1ea69261c6197e0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adoptive Transfer</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Blood Urea Nitrogen</topic><topic>Chemotaxis, Leukocyte</topic><topic>Cisplatin</topic><topic>Creatinine - blood</topic><topic>Disease Models, Animal</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Immunity, Innate</topic><topic>Inflammation Mediators - metabolism</topic><topic>Interleukin-1beta - metabolism</topic><topic>Interleukin-2 Receptor alpha Subunit - analysis</topic><topic>Kidney - immunology</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidney Diseases - blood</topic><topic>Kidney Diseases - chemically induced</topic><topic>Kidney Diseases - immunology</topic><topic>Kidney Diseases - pathology</topic><topic>Kidney Diseases - prevention & control</topic><topic>Macrophages - immunology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Nephrology. Urinary tract diseases</topic><topic>nephrotoxicity</topic><topic>regulatory T cell</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - transplantation</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - transplantation</topic><topic>Time Factors</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Hyojung</creatorcontrib><creatorcontrib>Nho, Dukhee</creatorcontrib><creatorcontrib>Chung, Hwan-Suck</creatorcontrib><creatorcontrib>Lee, Heekyung</creatorcontrib><creatorcontrib>Shin, Min-Kyu</creatorcontrib><creatorcontrib>Kim, Sung-Hoon</creatorcontrib><creatorcontrib>Bae, Hyunsu</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>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma 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</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</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 Central China</collection><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Hyojung</au><au>Nho, Dukhee</au><au>Chung, Hwan-Suck</au><au>Lee, Heekyung</au><au>Shin, Min-Kyu</au><au>Kim, Sung-Hoon</au><au>Bae, Hyunsu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD4+CD25+ regulatory T cells attenuate cisplatin-induced nephrotoxicity in mice</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>2010-12-01</date><risdate>2010</risdate><volume>78</volume><issue>11</issue><spage>1100</spage><epage>1109</epage><pages>1100-1109</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Nephrotoxicity limits the use of cisplatin, a widely used chemotherapeutic agent for treatment of various malignancies. Overall, CD4+ T cells mediate cisplatin-induced renal injury; however, the CD4+CD25+ regulatory T-cell subset (CD4+CD25+ Treg) has broad suppressive effects on many different cell types. In this study, we determined whether CD4+CD25+ Treg cells had protective effects against cisplatin-induced acute renal injury in nu/nu mice that lack mature T cells. In these mice, there was marked attenuation of the decreased survival, renal dysfunction and tubular injury, renal tumor necrosis factor-α, and interleukin-1β cytokine levels. Furthermore, renal macrophage accumulation was reduced in CD4+CD25+ Treg cell-adoptive transferred nu/nu mice compared with control mice. Infusion of CD4+CD25+Treg cells into wild-type Balb/c mice reduced serum blood urea nitrogen and creatinine levels equivalent to those in nu/nu mice and extended their survival time after cisplatin injection. In contrast, depletion of CD4+CD25+ Treg cells in wild-type mice exacerbated kidney injury after cisplatin administration. Transcription factor Foxp3-positive cells (Treg cells) were detected in the kidneys of nu/nu mice after cisplatin injection. Our results suggest that CD4+CD25+ Treg cells directly affect cisplatin nephrotoxicity and their modulation represents an additional treatment strategy.</abstract><cop>Basingstoke</cop><pub>Elsevier Inc</pub><pmid>20463654</pmid><doi>10.1038/ki.2010.139</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adoptive Transfer Animals Biological and medical sciences Biomarkers - blood Blood Urea Nitrogen Chemotaxis, Leukocyte Cisplatin Creatinine - blood Disease Models, Animal Forkhead Transcription Factors - metabolism Immunity, Innate Inflammation Mediators - metabolism Interleukin-1beta - metabolism Interleukin-2 Receptor alpha Subunit - analysis Kidney - immunology Kidney - metabolism Kidney - pathology Kidney Diseases - blood Kidney Diseases - chemically induced Kidney Diseases - immunology Kidney Diseases - pathology Kidney Diseases - prevention & control Macrophages - immunology Male Medical sciences Mice Mice, Inbred BALB C Mice, Nude Nephrology. Urinary tract diseases nephrotoxicity regulatory T cell T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - transplantation T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - transplantation Time Factors Tumor Necrosis Factor-alpha - metabolism |
| title | CD4+CD25+ regulatory T cells attenuate cisplatin-induced nephrotoxicity in mice |
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