Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease
Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission...
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| creator | Godoi, D F Cardoso, C R Ferraz, D B Provinciatto, P R Cunha, F Q Silva, J S Voltarelli, J C |
| description | Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4
+
leukocytes in the inflammatory infiltrate on days +7 and +14 and of CD8
+
cells on day +7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that high-dose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD. |
| doi_str_mv | 10.1038/bmt.2010.6 |
| format | Article |
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+
leukocytes in the inflammatory infiltrate on days +7 and +14 and of CD8
+
cells on day +7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that high-dose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.</description><identifier>ISSN: 0268-3369</identifier><identifier>EISSN: 1476-5365</identifier><identifier>DOI: 10.1038/bmt.2010.6</identifier><identifier>PMID: 20228850</identifier><identifier>CODEN: BMTRE9</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/347 ; 692/699/1503/257 ; 692/700/565/1436/99 ; 692/700/565/545/576/1955 ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Biological and medical sciences ; Bone marrow ; Bone Marrow Transplantation ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Care and treatment ; CD4 antigen ; CD4-Positive T-Lymphocytes - drug effects ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - pathology ; CD8 antigen ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; CD8-Positive T-Lymphocytes - pathology ; Cell Biology ; Chemotherapy ; Colitis ; Colitis - drug therapy ; Colitis - immunology ; Colitis - pathology ; Colitis - therapy ; Combined Modality Therapy ; Cyclosporine - administration & dosage ; Cyclosporine - therapeutic use ; Cytokines ; Cytokines - metabolism ; Diagnosis ; Dosage ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Health aspects ; Helper cells ; Hematology ; Hematopoietic Stem Cell Transplantation ; Hematopoietic stem cells ; Immune reconstitution ; Immune response ; Immunity, Mucosal - drug effects ; Immunology ; Immunosuppression ; Immunosuppression - methods ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - therapeutic use ; Inflammatory bowel disease ; Inflammatory bowel diseases ; Inflammatory Bowel Diseases - drug therapy ; Inflammatory Bowel Diseases - immunology ; Inflammatory Bowel Diseases - pathology ; Inflammatory Bowel Diseases - therapy ; Internal Medicine ; Intestine ; Leukocytes ; Lymphocytes T ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred BALB C ; Modulation ; Mucosal immunity ; original-article ; Other diseases. Semiology ; Public Health ; Remission ; Severity of Illness Index ; Stem cell transplantation ; Stem Cells ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Survival ; Survival Analysis ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Transplantation ; Trinitrobenzenesulfonic Acid - toxicity</subject><ispartof>Bone marrow transplantation (Basingstoke), 2010-10, Vol.45 (10), p.1562-1571</ispartof><rights>Macmillan Publishers Limited 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2010.</rights><rights>Copyright Nature Publishing Group Oct 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-1c503c75085b7152ee3b831168a6f6ce794b513f37d6304985dbd826c64b15493</citedby><cites>FETCH-LOGICAL-c541t-1c503c75085b7152ee3b831168a6f6ce794b513f37d6304985dbd826c64b15493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/bmt.2010.6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/bmt.2010.6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23336675$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20228850$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Godoi, D F</creatorcontrib><creatorcontrib>Cardoso, C R</creatorcontrib><creatorcontrib>Ferraz, D B</creatorcontrib><creatorcontrib>Provinciatto, P R</creatorcontrib><creatorcontrib>Cunha, F Q</creatorcontrib><creatorcontrib>Silva, J S</creatorcontrib><creatorcontrib>Voltarelli, J C</creatorcontrib><title>Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease</title><title>Bone marrow transplantation (Basingstoke)</title><addtitle>Bone Marrow Transplant</addtitle><addtitle>Bone Marrow Transplant</addtitle><description>Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4
+
leukocytes in the inflammatory infiltrate on days +7 and +14 and of CD8
+
cells on day +7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that high-dose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.</description><subject>631/250/347</subject><subject>692/699/1503/257</subject><subject>692/700/565/1436/99</subject><subject>692/700/565/545/576/1955</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone marrow</subject><subject>Bone Marrow Transplantation</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>Care and treatment</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - drug effects</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - pathology</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>CD8-Positive T-Lymphocytes - pathology</subject><subject>Cell Biology</subject><subject>Chemotherapy</subject><subject>Colitis</subject><subject>Colitis - drug therapy</subject><subject>Colitis - immunology</subject><subject>Colitis - pathology</subject><subject>Colitis - therapy</subject><subject>Combined Modality Therapy</subject><subject>Cyclosporine - administration & dosage</subject><subject>Cyclosporine - therapeutic use</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Diagnosis</subject><subject>Dosage</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Health aspects</subject><subject>Helper cells</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hematopoietic stem cells</subject><subject>Immune reconstitution</subject><subject>Immune response</subject><subject>Immunity, Mucosal - drug effects</subject><subject>Immunology</subject><subject>Immunosuppression</subject><subject>Immunosuppression - methods</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>Inflammatory Bowel Diseases - drug therapy</subject><subject>Inflammatory Bowel Diseases - immunology</subject><subject>Inflammatory Bowel Diseases - pathology</subject><subject>Inflammatory Bowel Diseases - therapy</subject><subject>Internal Medicine</subject><subject>Intestine</subject><subject>Leukocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Modulation</subject><subject>Mucosal immunity</subject><subject>original-article</subject><subject>Other diseases. Semiology</subject><subject>Public Health</subject><subject>Remission</subject><subject>Severity of Illness Index</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Transfusions. Complications. Transfusion reactions. 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Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone marrow</topic><topic>Bone Marrow Transplantation</topic><topic>Bone marrow, stem cells transplantation. Graft versus host reaction</topic><topic>Care and treatment</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - drug effects</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD4-Positive T-Lymphocytes - pathology</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - drug effects</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>CD8-Positive T-Lymphocytes - pathology</topic><topic>Cell Biology</topic><topic>Chemotherapy</topic><topic>Colitis</topic><topic>Colitis - drug therapy</topic><topic>Colitis - immunology</topic><topic>Colitis - pathology</topic><topic>Colitis - therapy</topic><topic>Combined Modality Therapy</topic><topic>Cyclosporine - administration & dosage</topic><topic>Cyclosporine - therapeutic use</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Diagnosis</topic><topic>Dosage</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Health aspects</topic><topic>Helper cells</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Hematopoietic stem cells</topic><topic>Immune reconstitution</topic><topic>Immune response</topic><topic>Immunity, Mucosal - drug effects</topic><topic>Immunology</topic><topic>Immunosuppression</topic><topic>Immunosuppression - methods</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Inflammatory bowel disease</topic><topic>Inflammatory bowel diseases</topic><topic>Inflammatory Bowel Diseases - drug therapy</topic><topic>Inflammatory Bowel Diseases - immunology</topic><topic>Inflammatory Bowel Diseases - pathology</topic><topic>Inflammatory Bowel Diseases - therapy</topic><topic>Internal Medicine</topic><topic>Intestine</topic><topic>Leukocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Modulation</topic><topic>Mucosal immunity</topic><topic>original-article</topic><topic>Other diseases. Semiology</topic><topic>Public Health</topic><topic>Remission</topic><topic>Severity of Illness Index</topic><topic>Stem cell transplantation</topic><topic>Stem Cells</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Transfusions. Complications. Transfusion reactions. 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Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4
+
leukocytes in the inflammatory infiltrate on days +7 and +14 and of CD8
+
cells on day +7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that high-dose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20228850</pmid><doi>10.1038/bmt.2010.6</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0268-3369 |
| ispartof | Bone marrow transplantation (Basingstoke), 2010-10, Vol.45 (10), p.1562-1571 |
| issn | 0268-3369 1476-5365 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_758133824 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 631/250/347 692/699/1503/257 692/700/565/1436/99 692/700/565/545/576/1955 Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Biological and medical sciences Bone marrow Bone Marrow Transplantation Bone marrow, stem cells transplantation. Graft versus host reaction Care and treatment CD4 antigen CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - pathology CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - pathology Cell Biology Chemotherapy Colitis Colitis - drug therapy Colitis - immunology Colitis - pathology Colitis - therapy Combined Modality Therapy Cyclosporine - administration & dosage Cyclosporine - therapeutic use Cytokines Cytokines - metabolism Diagnosis Dosage Female Gastroenterology. Liver. Pancreas. Abdomen Health aspects Helper cells Hematology Hematopoietic Stem Cell Transplantation Hematopoietic stem cells Immune reconstitution Immune response Immunity, Mucosal - drug effects Immunology Immunosuppression Immunosuppression - methods Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - therapeutic use Inflammatory bowel disease Inflammatory bowel diseases Inflammatory Bowel Diseases - drug therapy Inflammatory Bowel Diseases - immunology Inflammatory Bowel Diseases - pathology Inflammatory Bowel Diseases - therapy Internal Medicine Intestine Leukocytes Lymphocytes T Male Medical sciences Medicine Medicine & Public Health Mice Mice, Inbred BALB C Modulation Mucosal immunity original-article Other diseases. Semiology Public Health Remission Severity of Illness Index Stem cell transplantation Stem Cells Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Survival Survival Analysis Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplantation Trinitrobenzenesulfonic Acid - toxicity |
| title | Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T18%3A08%3A07IST&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=Hematopoietic%20SCT%20modulates%20gut%20inflammation%20in%20experimental%20inflammatory%20bowel%20disease&rft.jtitle=Bone%20marrow%20transplantation%20(Basingstoke)&rft.au=Godoi,%20D%20F&rft.date=2010-10-01&rft.volume=45&rft.issue=10&rft.spage=1562&rft.epage=1571&rft.pages=1562-1571&rft.issn=0268-3369&rft.eissn=1476-5365&rft.coden=BMTRE9&rft_id=info:doi/10.1038/bmt.2010.6&rft_dat=%3Cgale_proqu%3EA239816704%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=2642156266&rft_id=info:pmid/20228850&rft_galeid=A239816704&rfr_iscdi=true |