A combination regimen of low-dose bortezomib and rapamycin prolonged the graft survival in a murine allogeneic islet transplantation model.
Identifieur interne : 000401 ( Main/Exploration ); précédent : 000400; suivant : 000402A combination regimen of low-dose bortezomib and rapamycin prolonged the graft survival in a murine allogeneic islet transplantation model.
Auteurs : So-Hee Hong [Corée du Sud] ; Kihyun Kim [Corée du Sud] ; Jun-Seop Shin [Corée du Sud] ; Hyunwoo Chung [Corée du Sud] ; Chung-Gyu Park [Corée du Sud]Source :
- Immunology letters [ 1879-0542 ] ; 2019.
Descripteurs français
- KwdFr :
- Allogreffes (effets des médicaments et des substances chimiques), Allogreffes (immunologie), Animaux (MeSH), Antigènes d'histocompatibilité de classe II (immunologie), Antigènes d'histocompatibilité de classe II (métabolisme), Association de médicaments (méthodes), Bortézomib (administration et posologie), Cellules dendritiques (effets des médicaments et des substances chimiques), Cellules dendritiques (immunologie), Cellules dendritiques (métabolisme), Diabète expérimental (induit chimiquement), Diabète expérimental (thérapie), Facteurs de transcription Forkhead (immunologie), Facteurs de transcription Forkhead (métabolisme), Femelle (MeSH), Humains (MeSH), Immunosuppresseurs (administration et posologie), Inhibiteurs du protéasome (administration et posologie), Interféron gamma (immunologie), Interféron gamma (métabolisme), Lymphocytes T régulateurs (effets des médicaments et des substances chimiques), Lymphocytes T régulateurs (immunologie), Lymphocytes T régulateurs (métabolisme), Rate (cytologie), Rate (effets des médicaments et des substances chimiques), Rate (immunologie), Relation dose-effet des médicaments (MeSH), Sirolimus (administration et posologie), Souris (MeSH), Streptozocine (toxicité), Survie du greffon (effets des médicaments et des substances chimiques), Survie du greffon (immunologie), Tolérance immunitaire (effets des médicaments et des substances chimiques), Transplantation d'ilots de Langerhans (effets indésirables), Transplantation homologue (effets indésirables), Transplantation homologue (méthodes).
- MESH :
- administration et posologie : Bortézomib, Immunosuppresseurs, Inhibiteurs du protéasome, Sirolimus.
- cytologie : Rate.
- effets des médicaments et des substances chimiques : Allogreffes, Cellules dendritiques, Lymphocytes T régulateurs, Rate, Survie du greffon, Tolérance immunitaire.
- effets indésirables : Transplantation d'ilots de Langerhans, Transplantation homologue.
- immunologie : Allogreffes, Antigènes d'histocompatibilité de classe II, Cellules dendritiques, Facteurs de transcription Forkhead, Interféron gamma, Lymphocytes T régulateurs, Rate, Survie du greffon.
- induit chimiquement : Diabète expérimental.
- métabolisme : Antigènes d'histocompatibilité de classe II, Cellules dendritiques, Facteurs de transcription Forkhead, Interféron gamma, Lymphocytes T régulateurs.
- méthodes : Association de médicaments, Transplantation homologue.
- thérapie : Diabète expérimental.
- toxicité : Streptozocine.
- Animaux, Femelle, Humains, Relation dose-effet des médicaments, Souris.
English descriptors
- KwdEn :
- Allografts (drug effects), Allografts (immunology), Animals (MeSH), Bortezomib (administration & dosage), Dendritic Cells (drug effects), Dendritic Cells (immunology), Dendritic Cells (metabolism), Diabetes Mellitus, Experimental (chemically induced), Diabetes Mellitus, Experimental (therapy), Dose-Response Relationship, Drug (MeSH), Drug Therapy, Combination (methods), Female (MeSH), Forkhead Transcription Factors (immunology), Forkhead Transcription Factors (metabolism), Graft Survival (drug effects), Graft Survival (immunology), Histocompatibility Antigens Class II (immunology), Histocompatibility Antigens Class II (metabolism), Humans (MeSH), Immune Tolerance (drug effects), Immunosuppressive Agents (administration & dosage), Interferon-gamma (immunology), Interferon-gamma (metabolism), Islets of Langerhans Transplantation (adverse effects), Mice (MeSH), Proteasome Inhibitors (administration & dosage), Sirolimus (administration & dosage), Spleen (cytology), Spleen (drug effects), Spleen (immunology), Streptozocin (toxicity), T-Lymphocytes, Regulatory (drug effects), T-Lymphocytes, Regulatory (immunology), T-Lymphocytes, Regulatory (metabolism), Transplantation, Homologous (adverse effects), Transplantation, Homologous (methods).
- MESH :
- chemical , administration & dosage : Bortezomib, Immunosuppressive Agents, Proteasome Inhibitors, Sirolimus.
- adverse effects : Islets of Langerhans Transplantation, Transplantation, Homologous.
- chemically induced : Diabetes Mellitus, Experimental.
- cytology : Spleen.
- drug effects : Allografts, Dendritic Cells, Graft Survival, Immune Tolerance, Spleen, T-Lymphocytes, Regulatory.
- immunology : Allografts, Dendritic Cells, Forkhead Transcription Factors, Graft Survival, Histocompatibility Antigens Class II, Interferon-gamma, Spleen, T-Lymphocytes, Regulatory.
- metabolism : Dendritic Cells, Forkhead Transcription Factors, Histocompatibility Antigens Class II, Interferon-gamma, T-Lymphocytes, Regulatory.
- methods : Drug Therapy, Combination, Transplantation, Homologous.
- therapy : Diabetes Mellitus, Experimental.
- chemical , toxicity : Streptozocin.
- Animals, Dose-Response Relationship, Drug, Female, Humans, Mice.
Abstract
As the first FDA-approved proteasome inhibitor drug, bortezomib has been used for the treatment of multiple myeloma and lymphoma. However, its effects alone or in combination with other immunosuppressants on allogeneic islet transplantation have not been reported so far. In this study, we showed that the short-term combination treatment of low-dose bortezomib and rapamycin significantly prolonged the survival of islet allografts. Short-term treatment of low-dose (0.05 mg/kg or 0.1 mg/kg) bortezomib reduced the MHC class II expression in dendritic cells (DCs) of alloantigen-sensitized mice, and prolonged the islet allograft survival for up to 50 days in diabetic mice. Notably, when bortezomib was combined with rapamycin, it induced islet-specific immunological tolerance which allowed the acceptance of a second graft without additional immunosuppression. This regimen dramatically reduced the alloantigen-specific IFN-γ-producing T cells in the spleen, and increased regulatory T cells both at the graft site and in the spleen. Therefore, we propose that short-term treatment of low-dose bortezomib and rapamycin could be a new tolerance-promoting immunosuppressive regimen for allogeneic islet transplantation.
DOI: 10.1016/j.imlet.2019.10.005
PubMed: 31593743
Affiliations:
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Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080</wicri:regionArea><wicri:noRegion>03080</wicri:noRegion></affiliation></author><author><name sortKey="Park, Chung Gyu" sort="Park, Chung Gyu" uniqKey="Park C" first="Chung-Gyu" last="Park">Chung-Gyu Park</name><affiliation wicri:level="1"><nlm:affiliation>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. 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Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080</wicri:regionArea><wicri:noRegion>03080</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Kihyun" sort="Kim, Kihyun" uniqKey="Kim K" first="Kihyun" last="Kim">Kihyun Kim</name><affiliation wicri:level="1"><nlm:affiliation>Division of Hematology/Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea; Samsung Medical Center, Seoul, 06351, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Hematology/Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea; Samsung Medical Center, Seoul, 06351</wicri:regionArea><wicri:noRegion>06351</wicri:noRegion></affiliation></author><author><name sortKey="Shin, Jun Seop" sort="Shin, Jun Seop" uniqKey="Shin J" first="Jun-Seop" last="Shin">Jun-Seop Shin</name><affiliation wicri:level="1"><nlm:affiliation>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080</wicri:regionArea><wicri:noRegion>03080</wicri:noRegion></affiliation></author><author><name sortKey="Chung, Hyunwoo" sort="Chung, Hyunwoo" uniqKey="Chung H" first="Hyunwoo" last="Chung">Hyunwoo Chung</name><affiliation wicri:level="1"><nlm:affiliation>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080</wicri:regionArea><wicri:noRegion>03080</wicri:noRegion></affiliation></author><author><name sortKey="Park, Chung Gyu" sort="Park, Chung Gyu" uniqKey="Park C" first="Chung-Gyu" last="Park">Chung-Gyu Park</name><affiliation wicri:level="1"><nlm:affiliation>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. Electronic address: chgpark@snu.ac.kr.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080</wicri:regionArea><wicri:noRegion>03080</wicri:noRegion></affiliation></author></analytic><series><title level="j">Immunology letters</title><idno type="eISSN">1879-0542</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Allografts (drug effects)</term><term>Allografts (immunology)</term><term>Animals (MeSH)</term><term>Bortezomib (administration & dosage)</term><term>Dendritic Cells (drug effects)</term><term>Dendritic Cells (immunology)</term><term>Dendritic Cells (metabolism)</term><term>Diabetes Mellitus, Experimental (chemically induced)</term><term>Diabetes Mellitus, Experimental (therapy)</term><term>Dose-Response Relationship, Drug (MeSH)</term><term>Drug Therapy, Combination (methods)</term><term>Female (MeSH)</term><term>Forkhead Transcription Factors (immunology)</term><term>Forkhead Transcription Factors (metabolism)</term><term>Graft Survival (drug effects)</term><term>Graft Survival (immunology)</term><term>Histocompatibility Antigens Class II (immunology)</term><term>Histocompatibility Antigens Class II (metabolism)</term><term>Humans (MeSH)</term><term>Immune Tolerance (drug effects)</term><term>Immunosuppressive Agents (administration & dosage)</term><term>Interferon-gamma (immunology)</term><term>Interferon-gamma (metabolism)</term><term>Islets of Langerhans Transplantation (adverse effects)</term><term>Mice (MeSH)</term><term>Proteasome Inhibitors (administration & dosage)</term><term>Sirolimus (administration & dosage)</term><term>Spleen (cytology)</term><term>Spleen (drug effects)</term><term>Spleen (immunology)</term><term>Streptozocin (toxicity)</term><term>T-Lymphocytes, Regulatory (drug effects)</term><term>T-Lymphocytes, Regulatory (immunology)</term><term>T-Lymphocytes, Regulatory (metabolism)</term><term>Transplantation, Homologous (adverse effects)</term><term>Transplantation, Homologous (methods)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Allogreffes (effets des médicaments et des substances chimiques)</term><term>Allogreffes (immunologie)</term><term>Animaux (MeSH)</term><term>Antigènes d'histocompatibilité de classe II (immunologie)</term><term>Antigènes d'histocompatibilité de classe II (métabolisme)</term><term>Association de médicaments (méthodes)</term><term>Bortézomib (administration et posologie)</term><term>Cellules dendritiques (effets des médicaments et des substances chimiques)</term><term>Cellules dendritiques (immunologie)</term><term>Cellules dendritiques (métabolisme)</term><term>Diabète expérimental (induit chimiquement)</term><term>Diabète expérimental (thérapie)</term><term>Facteurs de transcription Forkhead (immunologie)</term><term>Facteurs de transcription Forkhead (métabolisme)</term><term>Femelle (MeSH)</term><term>Humains (MeSH)</term><term>Immunosuppresseurs (administration et posologie)</term><term>Inhibiteurs du protéasome (administration et posologie)</term><term>Interféron gamma (immunologie)</term><term>Interféron gamma (métabolisme)</term><term>Lymphocytes T régulateurs (effets des médicaments et des substances chimiques)</term><term>Lymphocytes T régulateurs (immunologie)</term><term>Lymphocytes T régulateurs (métabolisme)</term><term>Rate (cytologie)</term><term>Rate (effets des médicaments et des substances chimiques)</term><term>Rate (immunologie)</term><term>Relation dose-effet des médicaments (MeSH)</term><term>Sirolimus (administration et posologie)</term><term>Souris (MeSH)</term><term>Streptozocine (toxicité)</term><term>Survie du greffon (effets des médicaments et des substances chimiques)</term><term>Survie du greffon (immunologie)</term><term>Tolérance immunitaire (effets des médicaments et des substances chimiques)</term><term>Transplantation d'ilots de Langerhans (effets indésirables)</term><term>Transplantation homologue (effets indésirables)</term><term>Transplantation homologue (méthodes)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Bortezomib</term><term>Immunosuppressive Agents</term><term>Proteasome Inhibitors</term><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Bortézomib</term><term>Immunosuppresseurs</term><term>Inhibiteurs du protéasome</term><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Islets of Langerhans Transplantation</term><term>Transplantation, Homologous</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Diabetes Mellitus, Experimental</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Rate</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Spleen</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Allografts</term><term>Dendritic Cells</term><term>Graft Survival</term><term>Immune Tolerance</term><term>Spleen</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Allogreffes</term><term>Cellules dendritiques</term><term>Lymphocytes T régulateurs</term><term>Rate</term><term>Survie du greffon</term><term>Tolérance immunitaire</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Transplantation d'ilots de Langerhans</term><term>Transplantation homologue</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Allogreffes</term><term>Antigènes d'histocompatibilité de classe II</term><term>Cellules dendritiques</term><term>Facteurs de transcription Forkhead</term><term>Interféron gamma</term><term>Lymphocytes T régulateurs</term><term>Rate</term><term>Survie du greffon</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Allografts</term><term>Dendritic Cells</term><term>Forkhead Transcription Factors</term><term>Graft Survival</term><term>Histocompatibility Antigens Class II</term><term>Interferon-gamma</term><term>Spleen</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" qualifier="induit chimiquement" xml:lang="fr"><term>Diabète expérimental</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Dendritic Cells</term><term>Forkhead Transcription Factors</term><term>Histocompatibility Antigens Class II</term><term>Interferon-gamma</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Drug Therapy, Combination</term><term>Transplantation, Homologous</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes d'histocompatibilité de classe II</term><term>Cellules dendritiques</term><term>Facteurs de transcription Forkhead</term><term>Interféron gamma</term><term>Lymphocytes T régulateurs</term></keywords><keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Association de médicaments</term><term>Transplantation homologue</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Diabetes Mellitus, Experimental</term></keywords><keywords scheme="MESH" qualifier="thérapie" xml:lang="fr"><term>Diabète expérimental</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Streptozocin</term></keywords><keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Streptozocine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Dose-Response Relationship, Drug</term><term>Female</term><term>Humans</term><term>Mice</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Humains</term><term>Relation dose-effet des médicaments</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">As the first FDA-approved proteasome inhibitor drug, bortezomib has been used for the treatment of multiple myeloma and lymphoma. However, its effects alone or in combination with other immunosuppressants on allogeneic islet transplantation have not been reported so far. In this study, we showed that the short-term combination treatment of low-dose bortezomib and rapamycin significantly prolonged the survival of islet allografts. Short-term treatment of low-dose (0.05 mg/kg or 0.1 mg/kg) bortezomib reduced the MHC class II expression in dendritic cells (DCs) of alloantigen-sensitized mice, and prolonged the islet allograft survival for up to 50 days in diabetic mice. Notably, when bortezomib was combined with rapamycin, it induced islet-specific immunological tolerance which allowed the acceptance of a second graft without additional immunosuppression. This regimen dramatically reduced the alloantigen-specific IFN-γ-producing T cells in the spleen, and increased regulatory T cells both at the graft site and in the spleen. Therefore, we propose that short-term treatment of low-dose bortezomib and rapamycin could be a new tolerance-promoting immunosuppressive regimen for allogeneic islet transplantation.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31593743</PMID><DateCompleted><Year>2020</Year><Month>05</Month><Day>27</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>27</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1879-0542</ISSN><JournalIssue CitedMedium="Internet"><Volume>216</Volume><PubDate><Year>2019</Year><Month>12</Month></PubDate></JournalIssue><Title>Immunology letters</Title><ISOAbbreviation>Immunol Lett</ISOAbbreviation></Journal><ArticleTitle>A combination regimen of low-dose bortezomib and rapamycin prolonged the graft survival in a murine allogeneic islet transplantation model.</ArticleTitle><Pagination><MedlinePgn>21-27</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0165-2478(19)30361-X</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.imlet.2019.10.005</ELocationID><Abstract><AbstractText>As the first FDA-approved proteasome inhibitor drug, bortezomib has been used for the treatment of multiple myeloma and lymphoma. However, its effects alone or in combination with other immunosuppressants on allogeneic islet transplantation have not been reported so far. In this study, we showed that the short-term combination treatment of low-dose bortezomib and rapamycin significantly prolonged the survival of islet allografts. Short-term treatment of low-dose (0.05 mg/kg or 0.1 mg/kg) bortezomib reduced the MHC class II expression in dendritic cells (DCs) of alloantigen-sensitized mice, and prolonged the islet allograft survival for up to 50 days in diabetic mice. Notably, when bortezomib was combined with rapamycin, it induced islet-specific immunological tolerance which allowed the acceptance of a second graft without additional immunosuppression. This regimen dramatically reduced the alloantigen-specific IFN-γ-producing T cells in the spleen, and increased regulatory T cells both at the graft site and in the spleen. Therefore, we propose that short-term treatment of low-dose bortezomib and rapamycin could be a new tolerance-promoting immunosuppressive regimen for allogeneic islet transplantation.</AbstractText><CopyrightInformation>Copyright © 2019. Published by Elsevier B.V.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hong</LastName><ForeName>So-Hee</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Kihyun</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Division of Hematology/Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea; Samsung Medical Center, Seoul, 06351, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shin</LastName><ForeName>Jun-Seop</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chung</LastName><ForeName>Hyunwoo</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Chung-Gyu</ForeName><Initials>CG</Initials><AffiliationInfo><Affiliation>Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. Electronic address: chgpark@snu.ac.kr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>10</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Immunol Lett</MedlineTA><NlmUniqueID>7910006</NlmUniqueID><ISSNLinking>0165-2478</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051858">Forkhead Transcription Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C498833">Foxp3 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000949">Histocompatibility Antigens Class II</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000611649">IFNG protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007166">Immunosuppressive Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D061988">Proteasome Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>5W494URQ81</RegistryNumber><NameOfSubstance UI="D013311">Streptozocin</NameOfSubstance></Chemical><Chemical><RegistryNumber>69G8BD63PP</RegistryNumber><NameOfSubstance UI="D000069286">Bortezomib</NameOfSubstance></Chemical><Chemical><RegistryNumber>82115-62-6</RegistryNumber><NameOfSubstance UI="D007371">Interferon-gamma</NameOfSubstance></Chemical><Chemical><RegistryNumber>W36ZG6FT64</RegistryNumber><NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D064591" MajorTopicYN="N">Allografts</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000069286" MajorTopicYN="N">Bortezomib</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003921" MajorTopicYN="N">Diabetes Mellitus, Experimental</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004359" MajorTopicYN="N">Drug Therapy, Combination</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051858" MajorTopicYN="N">Forkhead Transcription Factors</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006085" MajorTopicYN="N">Graft Survival</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000949" MajorTopicYN="N">Histocompatibility Antigens Class II</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007108" MajorTopicYN="N">Immune Tolerance</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007166" MajorTopicYN="N">Immunosuppressive Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007371" MajorTopicYN="N">Interferon-gamma</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016381" MajorTopicYN="N">Islets of Langerhans Transplantation</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D061988" MajorTopicYN="N">Proteasome Inhibitors</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013154" MajorTopicYN="N">Spleen</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013311" MajorTopicYN="N">Streptozocin</DescriptorName><QualifierName UI="Q000633" MajorTopicYN="N">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050378" MajorTopicYN="N">T-Lymphocytes, Regulatory</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014184" MajorTopicYN="N">Transplantation, Homologous</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Bortezomib</Keyword><Keyword MajorTopicYN="Y">Islet transplantation</Keyword><Keyword MajorTopicYN="Y">Rapamycin</Keyword><Keyword MajorTopicYN="Y">Tolerance</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>07</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>09</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>10</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>10</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>5</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>10</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31593743</ArticleId><ArticleId IdType="pii">S0165-2478(19)30361-X</ArticleId><ArticleId IdType="doi">10.1016/j.imlet.2019.10.005</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Corée du Sud</li></country></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Hong, So Hee" sort="Hong, So Hee" uniqKey="Hong S" first="So-Hee" last="Hong">So-Hee Hong</name></noRegion><name sortKey="Chung, Hyunwoo" sort="Chung, Hyunwoo" uniqKey="Chung H" first="Hyunwoo" last="Chung">Hyunwoo Chung</name><name sortKey="Kim, Kihyun" sort="Kim, Kihyun" uniqKey="Kim K" first="Kihyun" last="Kim">Kihyun Kim</name><name sortKey="Park, Chung Gyu" sort="Park, Chung Gyu" uniqKey="Park C" first="Chung-Gyu" last="Park">Chung-Gyu Park</name><name sortKey="Shin, Jun Seop" sort="Shin, Jun Seop" uniqKey="Shin J" first="Jun-Seop" last="Shin">Jun-Seop Shin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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