Prevention of Type 1 Diabetes with Acetalated Dextran Microparticles Containing Rapamycin and Pancreatic Peptide P31.
Identifieur interne : 000517 ( Main/Exploration ); précédent : 000516; suivant : 000518Prevention of Type 1 Diabetes with Acetalated Dextran Microparticles Containing Rapamycin and Pancreatic Peptide P31.
Auteurs : Naihan Chen [États-Unis] ; Charles J. Kroger [États-Unis] ; Roland M. Tisch [États-Unis] ; Eric M. Bachelder [États-Unis] ; Kristy M. Ainslie [États-Unis]Source :
- Advanced healthcare materials [ 2192-2659 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Cellules cultivées (MeSH), Cellules à insuline (effets des médicaments et des substances chimiques), Cellules à insuline (métabolisme), Cytométrie en flux (MeSH), Dextrane (composition chimique), Diabète de type 1 (métabolisme), Diabète de type 1 (prévention et contrôle), Facteurs de transcription Forkhead (génétique), Facteurs de transcription Forkhead (métabolisme), Femelle (MeSH), Interféron gamma (métabolisme), Interleukine-2 (métabolisme), Lymphocytes T CD4+ (effets des médicaments et des substances chimiques), Lymphocytes T CD4+ (métabolisme), Polypeptide pancréatique (administration et posologie), Polypeptide pancréatique (composition chimique), Prolifération cellulaire (effets des médicaments et des substances chimiques), Sirolimus (administration et posologie), Sirolimus (composition chimique), Sirolimus (usage thérapeutique), Souris (MeSH), Souris de lignée BALB C (MeSH).
- MESH :
- administration et posologie : Polypeptide pancréatique, Sirolimus.
- composition chimique : Dextrane, Polypeptide pancréatique, Sirolimus.
- effets des médicaments et des substances chimiques : Cellules à insuline, Lymphocytes T CD4+, Prolifération cellulaire.
- génétique : Facteurs de transcription Forkhead.
- métabolisme : Cellules à insuline, Diabète de type 1, Facteurs de transcription Forkhead, Interféron gamma, Interleukine-2, Lymphocytes T CD4+.
- prévention et contrôle : Diabète de type 1.
- usage thérapeutique : Sirolimus.
- Animaux, Cellules cultivées, Cytométrie en flux, Femelle, Souris, Souris de lignée BALB C.
English descriptors
- KwdEn :
- Animals (MeSH), CD4-Positive T-Lymphocytes (drug effects), CD4-Positive T-Lymphocytes (metabolism), Cell Proliferation (drug effects), Cells, Cultured (MeSH), Dextrans (chemistry), Diabetes Mellitus, Type 1 (metabolism), Diabetes Mellitus, Type 1 (prevention & control), Female (MeSH), Flow Cytometry (MeSH), Forkhead Transcription Factors (genetics), Forkhead Transcription Factors (metabolism), Insulin-Secreting Cells (drug effects), Insulin-Secreting Cells (metabolism), Interferon-gamma (metabolism), Interleukin-2 (metabolism), Mice (MeSH), Mice, Inbred BALB C (MeSH), Pancreatic Polypeptide (administration & dosage), Pancreatic Polypeptide (chemistry), Sirolimus (administration & dosage), Sirolimus (chemistry), Sirolimus (therapeutic use).
- MESH :
- chemical , administration & dosage : Pancreatic Polypeptide, Sirolimus.
- chemical , chemistry : Dextrans, Pancreatic Polypeptide, Sirolimus.
- drug effects : CD4-Positive T-Lymphocytes, Cell Proliferation, Insulin-Secreting Cells.
- chemical , genetics : Forkhead Transcription Factors.
- metabolism : CD4-Positive T-Lymphocytes, Diabetes Mellitus, Type 1, Forkhead Transcription Factors, Insulin-Secreting Cells, Interferon-gamma, Interleukin-2.
- prevention & control : Diabetes Mellitus, Type 1.
- chemical , therapeutic use : Sirolimus.
- Animals, Cells, Cultured, Female, Flow Cytometry, Mice, Mice, Inbred BALB C.
Abstract
Type 1 diabetes (T1D) is a common autoimmune disease with no cure. T1D subjects are dependent on daily exogenous insulin administration, due to the loss of functional insulin-producing β cells. Needed are immunotherapies that prevent and/or treat T1D. One approach of immunotherapy is to administer an autoantigen to selectively tolerize diabetogenic effector T cells without global immunosuppression. To date, however, strategies of antigen-specific immunotherapy are largely ineffective in the clinic. Using an antigen-specific approach, a biodegradable polymeric delivery vehicle, acetalated dextran microparticles (Ace-DEX MPs), is applied and T1D development is prevented through coadministration of the immunosuppressant rapamycin and the diabetogenic peptide P31 (Rapa/P31/MPs), via alterations of both innate and adaptive immunity. Ex vivo, adoptively transferred CD4+ T cells exhibit reduced proliferation and an increased ratio of FoxP3+ to IFNγ+ T cells. In vitro analysis indicates dendritic cells exhibit a less mature phenotype following coculture with Rapa/P31/MPs, which results in reduced CD4+ T cell proliferation and proinflammatory cytokine production (IFNγ and IL-2), but promotes PD-1 expression. Together these results demonstrate Ace-DEX MP-based antigen-specific therapy effectively tolerizes diabetogenic CD4+ T cells to prevent T1D, thereby demonstrating one of the first successful attempts of T1D prevention using a single-formulation particulate delivery platform.
DOI: 10.1002/adhm.201800341
PubMed: 30051618
Affiliations:
- États-Unis
- Caroline du Nord
- Chapel Hill (Caroline du Nord)
- Université de Caroline du Nord à Chapel Hill
Links toward previous steps (curation, corpus...)
Le document en format XML
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xml:lang="en"><term>Animals (MeSH)</term><term>CD4-Positive T-Lymphocytes (drug effects)</term><term>CD4-Positive T-Lymphocytes (metabolism)</term><term>Cell Proliferation (drug effects)</term><term>Cells, Cultured (MeSH)</term><term>Dextrans (chemistry)</term><term>Diabetes Mellitus, Type 1 (metabolism)</term><term>Diabetes Mellitus, Type 1 (prevention & control)</term><term>Female (MeSH)</term><term>Flow Cytometry (MeSH)</term><term>Forkhead Transcription Factors (genetics)</term><term>Forkhead Transcription Factors (metabolism)</term><term>Insulin-Secreting Cells (drug effects)</term><term>Insulin-Secreting Cells (metabolism)</term><term>Interferon-gamma (metabolism)</term><term>Interleukin-2 (metabolism)</term><term>Mice (MeSH)</term><term>Mice, Inbred BALB C (MeSH)</term><term>Pancreatic Polypeptide (administration & dosage)</term><term>Pancreatic Polypeptide (chemistry)</term><term>Sirolimus (administration & dosage)</term><term>Sirolimus (chemistry)</term><term>Sirolimus (therapeutic use)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Cellules cultivées (MeSH)</term><term>Cellules à insuline (effets des médicaments et des substances chimiques)</term><term>Cellules à insuline (métabolisme)</term><term>Cytométrie en flux (MeSH)</term><term>Dextrane (composition chimique)</term><term>Diabète de type 1 (métabolisme)</term><term>Diabète de type 1 (prévention et contrôle)</term><term>Facteurs de transcription Forkhead (génétique)</term><term>Facteurs de transcription Forkhead (métabolisme)</term><term>Femelle (MeSH)</term><term>Interféron gamma (métabolisme)</term><term>Interleukine-2 (métabolisme)</term><term>Lymphocytes T CD4+ (effets des médicaments et des substances chimiques)</term><term>Lymphocytes T CD4+ (métabolisme)</term><term>Polypeptide pancréatique (administration et posologie)</term><term>Polypeptide pancréatique (composition chimique)</term><term>Prolifération cellulaire (effets des médicaments et des substances chimiques)</term><term>Sirolimus (administration et posologie)</term><term>Sirolimus (composition chimique)</term><term>Sirolimus (usage thérapeutique)</term><term>Souris (MeSH)</term><term>Souris de lignée BALB C (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Pancreatic Polypeptide</term><term>Sirolimus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Dextrans</term><term>Pancreatic Polypeptide</term><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Polypeptide pancréatique</term><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Dextrane</term><term>Polypeptide pancréatique</term><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Cell Proliferation</term><term>Insulin-Secreting Cells</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Cellules à insuline</term><term>Lymphocytes T CD4+</term><term>Prolifération cellulaire</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Forkhead Transcription Factors</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteurs de transcription Forkhead</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Diabetes Mellitus, Type 1</term><term>Forkhead Transcription Factors</term><term>Insulin-Secreting Cells</term><term>Interferon-gamma</term><term>Interleukin-2</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules à insuline</term><term>Diabète de type 1</term><term>Facteurs de transcription Forkhead</term><term>Interféron gamma</term><term>Interleukine-2</term><term>Lymphocytes T CD4+</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Diabetes Mellitus, Type 1</term></keywords><keywords scheme="MESH" qualifier="prévention et contrôle" xml:lang="fr"><term>Diabète de type 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Sirolimus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Female</term><term>Flow Cytometry</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Cytométrie en flux</term><term>Femelle</term><term>Souris</term><term>Souris de lignée BALB C</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Type 1 diabetes (T1D) is a common autoimmune disease with no cure. T1D subjects are dependent on daily exogenous insulin administration, due to the loss of functional insulin-producing β cells. Needed are immunotherapies that prevent and/or treat T1D. One approach of immunotherapy is to administer an autoantigen to selectively tolerize diabetogenic effector T cells without global immunosuppression. To date, however, strategies of antigen-specific immunotherapy are largely ineffective in the clinic. Using an antigen-specific approach, a biodegradable polymeric delivery vehicle, acetalated dextran microparticles (Ace-DEX MPs), is applied and T1D development is prevented through coadministration of the immunosuppressant rapamycin and the diabetogenic peptide P31 (Rapa/P31/MPs), via alterations of both innate and adaptive immunity. Ex vivo, adoptively transferred CD4<sup>+</sup> T cells exhibit reduced proliferation and an increased ratio of FoxP3<sup>+</sup> to IFNγ<sup>+</sup> T cells. In vitro analysis indicates dendritic cells exhibit a less mature phenotype following coculture with Rapa/P31/MPs, which results in reduced CD4<sup>+</sup> T cell proliferation and proinflammatory cytokine production (IFNγ and IL-2), but promotes PD-1 expression. Together these results demonstrate Ace-DEX MP-based antigen-specific therapy effectively tolerizes diabetogenic CD4<sup>+</sup> T cells to prevent T1D, thereby demonstrating one of the first successful attempts of T1D prevention using a single-formulation particulate delivery platform.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30051618</PMID><DateCompleted><Year>2019</Year><Month>11</Month><Day>08</Day></DateCompleted><DateRevised><Year>2019</Year><Month>11</Month><Day>08</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2192-2659</ISSN><JournalIssue CitedMedium="Internet"><Volume>7</Volume><Issue>18</Issue><PubDate><Year>2018</Year><Month>09</Month></PubDate></JournalIssue><Title>Advanced healthcare materials</Title><ISOAbbreviation>Adv Healthc Mater</ISOAbbreviation></Journal><ArticleTitle>Prevention of Type 1 Diabetes with Acetalated Dextran Microparticles Containing Rapamycin and Pancreatic Peptide P31.</ArticleTitle><Pagination><MedlinePgn>e1800341</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/adhm.201800341</ELocationID><Abstract><AbstractText>Type 1 diabetes (T1D) is a common autoimmune disease with no cure. T1D subjects are dependent on daily exogenous insulin administration, due to the loss of functional insulin-producing β cells. Needed are immunotherapies that prevent and/or treat T1D. One approach of immunotherapy is to administer an autoantigen to selectively tolerize diabetogenic effector T cells without global immunosuppression. To date, however, strategies of antigen-specific immunotherapy are largely ineffective in the clinic. Using an antigen-specific approach, a biodegradable polymeric delivery vehicle, acetalated dextran microparticles (Ace-DEX MPs), is applied and T1D development is prevented through coadministration of the immunosuppressant rapamycin and the diabetogenic peptide P31 (Rapa/P31/MPs), via alterations of both innate and adaptive immunity. Ex vivo, adoptively transferred CD4<sup>+</sup> T cells exhibit reduced proliferation and an increased ratio of FoxP3<sup>+</sup> to IFNγ<sup>+</sup> T cells. In vitro analysis indicates dendritic cells exhibit a less mature phenotype following coculture with Rapa/P31/MPs, which results in reduced CD4<sup>+</sup> T cell proliferation and proinflammatory cytokine production (IFNγ and IL-2), but promotes PD-1 expression. Together these results demonstrate Ace-DEX MP-based antigen-specific therapy effectively tolerizes diabetogenic CD4<sup>+</sup> T cells to prevent T1D, thereby demonstrating one of the first successful attempts of T1D prevention using a single-formulation particulate delivery platform.</AbstractText><CopyrightInformation>© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Naihan</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0002-7145-0776</Identifier><AffiliationInfo><Affiliation>Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kroger</LastName><ForeName>Charles J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tisch</LastName><ForeName>Roland M</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bachelder</LastName><ForeName>Eric M</ForeName><Initials>EM</Initials><AffiliationInfo><Affiliation>Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ainslie</LastName><ForeName>Kristy M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>1-SRA-2015-12-Q-R</GrantID><Acronym>JDRF</Acronym><Agency>Juvenile Diabetes Research Foundation</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA016086</GrantID><Acronym>NH</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>07</Month><Day>26</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Adv Healthc Mater</MedlineTA><NlmUniqueID>101581613</NlmUniqueID><ISSNLinking>2192-2640</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D003911">Dextrans</NameOfSubstance></Chemical><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="D007376">Interleukin-2</NameOfSubstance></Chemical><Chemical><RegistryNumber>59763-91-6</RegistryNumber><NameOfSubstance UI="D010191">Pancreatic Polypeptide</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="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003911" MajorTopicYN="N">Dextrans</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003922" MajorTopicYN="N">Diabetes Mellitus, Type 1</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005434" MajorTopicYN="N">Flow 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MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010191" MajorTopicYN="N">Pancreatic Polypeptide</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">autoimmune disease</Keyword><Keyword MajorTopicYN="Y">drug delivery</Keyword><Keyword MajorTopicYN="Y">immunotherapy</Keyword><Keyword MajorTopicYN="Y">microparticles</Keyword><Keyword MajorTopicYN="Y">tolerance</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>04</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>7</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>11</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>7</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30051618</ArticleId><ArticleId IdType="doi">10.1002/adhm.201800341</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li></region><settlement><li>Chapel Hill (Caroline du Nord)</li></settlement><orgName><li>Université de Caroline du Nord à Chapel Hill</li></orgName></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Chen, Naihan" sort="Chen, Naihan" uniqKey="Chen N" first="Naihan" last="Chen">Naihan Chen</name></region><name sortKey="Ainslie, Kristy M" sort="Ainslie, Kristy M" uniqKey="Ainslie K" first="Kristy M" last="Ainslie">Kristy M. Ainslie</name><name sortKey="Bachelder, Eric M" sort="Bachelder, Eric M" uniqKey="Bachelder E" first="Eric M" last="Bachelder">Eric M. Bachelder</name><name sortKey="Kroger, Charles J" sort="Kroger, Charles J" uniqKey="Kroger C" first="Charles J" last="Kroger">Charles J. Kroger</name><name sortKey="Tisch, Roland M" sort="Tisch, Roland M" uniqKey="Tisch R" first="Roland M" last="Tisch">Roland M. Tisch</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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