T cells and macrophages responding to oxidative damage cooperate in pathogenesis of a mouse model of age-related macular degeneration.
Identifieur interne : 000E89 ( Main/Corpus ); précédent : 000E88; suivant : 000E90T cells and macrophages responding to oxidative damage cooperate in pathogenesis of a mouse model of age-related macular degeneration.
Auteurs : Fernando Cruz-Guilloty ; Ali M. Saeed ; Stephanie Duffort ; Marisol Cano ; Katayoon B. Ebrahimi ; Asha Ballmick ; Yaohong Tan ; Hua Wang ; James M. Laird ; Robert G. Salomon ; James T. Handa ; Victor L. PerezSource :
- PloS one [ 1932-6203 ] ; 2014.
English descriptors
- KwdEn :
- Animals (MeSH), Biological Transport (drug effects), Cyclosporine (pharmacology), Disease Models, Animal (MeSH), Female (MeSH), Humans (MeSH), Immunization (MeSH), Interferon-gamma (biosynthesis), Interleukin-7 (biosynthesis), Macrophages (cytology), Macrophages (immunology), Macular Degeneration (etiology), Macular Degeneration (immunology), Macular Degeneration (metabolism), Male (MeSH), Mice (MeSH), Oxidative Stress (immunology), Pyrroles (metabolism), Retinal Pigment Epithelium (drug effects), Retinal Pigment Epithelium (immunology), Retinal Pigment Epithelium (metabolism), Sirolimus (pharmacology), T-Lymphocytes (cytology), T-Lymphocytes (immunology).
- MESH :
- chemical , biosynthesis : Interferon-gamma, Interleukin-7.
- chemical , metabolism : Pyrroles.
- chemical , pharmacology : Cyclosporine, Sirolimus.
- cytology : Macrophages, T-Lymphocytes.
- drug effects : Biological Transport, Retinal Pigment Epithelium.
- etiology : Macular Degeneration.
- immunology : Macrophages, Macular Degeneration, Oxidative Stress, Retinal Pigment Epithelium, T-Lymphocytes.
- metabolism : Macular Degeneration, Retinal Pigment Epithelium.
- Animals, Disease Models, Animal, Female, Humans, Immunization, Male, Mice.
Abstract
Age-related macular degeneration (AMD) is a major disease affecting central vision, but the pathogenic mechanisms are not fully understood. Using a mouse model, we examined the relationship of two factors implicated in AMD development: oxidative stress and the immune system. Carboxyethylpyrrole (CEP) is a lipid peroxidation product associated with AMD in humans and AMD-like pathology in mice. Previously, we demonstrated that CEP immunization leads to retinal infiltration of pro-inflammatory M1 macrophages before overt retinal degeneration. Here, we provide direct and indirect mechanisms for the effect of CEP on macrophages, and show for the first time that antigen-specific T cells play a leading role in AMD pathogenesis. In vitro, CEP directly induced M1 macrophage polarization and production of M1-related factors by retinal pigment epithelial (RPE) cells. In vivo, CEP eye injections in mice induced acute pro-inflammatory gene expression in the retina and human AMD eyes showed distinctively diffuse CEP immunolabeling within RPE cells. Importantly, interferon-gamma (IFN-γ) and interleukin-17 (IL-17)-producing CEP-specific T cells were identified ex vivo after CEP immunization and promoted M1 polarization in co-culture experiments. Finally, T cell immunosuppressive therapy inhibited CEP-mediated pathology. These data indicate that T cells and M1 macrophages activated by oxidative damage cooperate in AMD pathogenesis.
DOI: 10.1371/journal.pone.0088201
PubMed: 24586307
PubMed Central: PMC3929609
Links to Exploration step
pubmed:24586307Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">T cells and macrophages responding to oxidative damage cooperate in pathogenesis of a mouse model of age-related macular degeneration.</title><author><name sortKey="Cruz Guilloty, Fernando" sort="Cruz Guilloty, Fernando" uniqKey="Cruz Guilloty F" first="Fernando" last="Cruz-Guilloty">Fernando Cruz-Guilloty</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America ; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Saeed, Ali M" sort="Saeed, Ali M" uniqKey="Saeed A" first="Ali M" last="Saeed">Ali M. Saeed</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Duffort, Stephanie" sort="Duffort, Stephanie" uniqKey="Duffort S" first="Stephanie" last="Duffort">Stephanie Duffort</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Cano, Marisol" sort="Cano, Marisol" uniqKey="Cano M" first="Marisol" last="Cano">Marisol Cano</name><affiliation><nlm:affiliation>Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ebrahimi, Katayoon B" sort="Ebrahimi, Katayoon B" uniqKey="Ebrahimi K" first="Katayoon B" last="Ebrahimi">Katayoon B. Ebrahimi</name><affiliation><nlm:affiliation>Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ballmick, Asha" sort="Ballmick, Asha" uniqKey="Ballmick A" first="Asha" last="Ballmick">Asha Ballmick</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Tan, Yaohong" sort="Tan, Yaohong" uniqKey="Tan Y" first="Yaohong" last="Tan">Yaohong Tan</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Hua" sort="Wang, Hua" uniqKey="Wang H" first="Hua" last="Wang">Hua Wang</name><affiliation><nlm:affiliation>Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Laird, James M" sort="Laird, James M" uniqKey="Laird J" first="James M" last="Laird">James M. Laird</name><affiliation><nlm:affiliation>Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Salomon, Robert G" sort="Salomon, Robert G" uniqKey="Salomon R" first="Robert G" last="Salomon">Robert G. Salomon</name><affiliation><nlm:affiliation>Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Handa, James T" sort="Handa, James T" uniqKey="Handa J" first="James T" last="Handa">James T. Handa</name><affiliation><nlm:affiliation>Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Perez, Victor L" sort="Perez, Victor L" uniqKey="Perez V" first="Victor L" last="Perez">Victor L. Perez</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America ; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24586307</idno><idno type="pmid">24586307</idno><idno type="doi">10.1371/journal.pone.0088201</idno><idno type="pmc">PMC3929609</idno><idno type="wicri:Area/Main/Corpus">000E89</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000E89</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">T cells and macrophages responding to oxidative damage cooperate in pathogenesis of a mouse model of age-related macular degeneration.</title><author><name sortKey="Cruz Guilloty, Fernando" sort="Cruz Guilloty, Fernando" uniqKey="Cruz Guilloty F" first="Fernando" last="Cruz-Guilloty">Fernando Cruz-Guilloty</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America ; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Saeed, Ali M" sort="Saeed, Ali M" uniqKey="Saeed A" first="Ali M" last="Saeed">Ali M. Saeed</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Duffort, Stephanie" sort="Duffort, Stephanie" uniqKey="Duffort S" first="Stephanie" last="Duffort">Stephanie Duffort</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Cano, Marisol" sort="Cano, Marisol" uniqKey="Cano M" first="Marisol" last="Cano">Marisol Cano</name><affiliation><nlm:affiliation>Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ebrahimi, Katayoon B" sort="Ebrahimi, Katayoon B" uniqKey="Ebrahimi K" first="Katayoon B" last="Ebrahimi">Katayoon B. Ebrahimi</name><affiliation><nlm:affiliation>Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ballmick, Asha" sort="Ballmick, Asha" uniqKey="Ballmick A" first="Asha" last="Ballmick">Asha Ballmick</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Tan, Yaohong" sort="Tan, Yaohong" uniqKey="Tan Y" first="Yaohong" last="Tan">Yaohong Tan</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Hua" sort="Wang, Hua" uniqKey="Wang H" first="Hua" last="Wang">Hua Wang</name><affiliation><nlm:affiliation>Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Laird, James M" sort="Laird, James M" uniqKey="Laird J" first="James M" last="Laird">James M. Laird</name><affiliation><nlm:affiliation>Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Salomon, Robert G" sort="Salomon, Robert G" uniqKey="Salomon R" first="Robert G" last="Salomon">Robert G. Salomon</name><affiliation><nlm:affiliation>Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Handa, James T" sort="Handa, James T" uniqKey="Handa J" first="James T" last="Handa">James T. Handa</name><affiliation><nlm:affiliation>Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Perez, Victor L" sort="Perez, Victor L" uniqKey="Perez V" first="Victor L" last="Perez">Victor L. Perez</name><affiliation><nlm:affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America ; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</nlm:affiliation></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Biological Transport (drug effects)</term><term>Cyclosporine (pharmacology)</term><term>Disease Models, Animal (MeSH)</term><term>Female (MeSH)</term><term>Humans (MeSH)</term><term>Immunization (MeSH)</term><term>Interferon-gamma (biosynthesis)</term><term>Interleukin-7 (biosynthesis)</term><term>Macrophages (cytology)</term><term>Macrophages (immunology)</term><term>Macular Degeneration (etiology)</term><term>Macular Degeneration (immunology)</term><term>Macular Degeneration (metabolism)</term><term>Male (MeSH)</term><term>Mice (MeSH)</term><term>Oxidative Stress (immunology)</term><term>Pyrroles (metabolism)</term><term>Retinal Pigment Epithelium (drug effects)</term><term>Retinal Pigment Epithelium (immunology)</term><term>Retinal Pigment Epithelium (metabolism)</term><term>Sirolimus (pharmacology)</term><term>T-Lymphocytes (cytology)</term><term>T-Lymphocytes (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Interferon-gamma</term><term>Interleukin-7</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Pyrroles</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Cyclosporine</term><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Macrophages</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Biological Transport</term><term>Retinal Pigment Epithelium</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Macular Degeneration</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Macrophages</term><term>Macular Degeneration</term><term>Oxidative Stress</term><term>Retinal Pigment Epithelium</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Macular Degeneration</term><term>Retinal Pigment Epithelium</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Immunization</term><term>Male</term><term>Mice</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Age-related macular degeneration (AMD) is a major disease affecting central vision, but the pathogenic mechanisms are not fully understood. Using a mouse model, we examined the relationship of two factors implicated in AMD development: oxidative stress and the immune system. Carboxyethylpyrrole (CEP) is a lipid peroxidation product associated with AMD in humans and AMD-like pathology in mice. Previously, we demonstrated that CEP immunization leads to retinal infiltration of pro-inflammatory M1 macrophages before overt retinal degeneration. Here, we provide direct and indirect mechanisms for the effect of CEP on macrophages, and show for the first time that antigen-specific T cells play a leading role in AMD pathogenesis. In vitro, CEP directly induced M1 macrophage polarization and production of M1-related factors by retinal pigment epithelial (RPE) cells. In vivo, CEP eye injections in mice induced acute pro-inflammatory gene expression in the retina and human AMD eyes showed distinctively diffuse CEP immunolabeling within RPE cells. Importantly, interferon-gamma (IFN-γ) and interleukin-17 (IL-17)-producing CEP-specific T cells were identified ex vivo after CEP immunization and promoted M1 polarization in co-culture experiments. Finally, T cell immunosuppressive therapy inhibited CEP-mediated pathology. These data indicate that T cells and M1 macrophages activated by oxidative damage cooperate in AMD pathogenesis. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24586307</PMID><DateCompleted><Year>2014</Year><Month>12</Month><Day>28</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>2</Issue><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS One</ISOAbbreviation></Journal><ArticleTitle>T cells and macrophages responding to oxidative damage cooperate in pathogenesis of a mouse model of age-related macular degeneration.</ArticleTitle><Pagination><MedlinePgn>e88201</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0088201</ELocationID><Abstract><AbstractText>Age-related macular degeneration (AMD) is a major disease affecting central vision, but the pathogenic mechanisms are not fully understood. Using a mouse model, we examined the relationship of two factors implicated in AMD development: oxidative stress and the immune system. Carboxyethylpyrrole (CEP) is a lipid peroxidation product associated with AMD in humans and AMD-like pathology in mice. Previously, we demonstrated that CEP immunization leads to retinal infiltration of pro-inflammatory M1 macrophages before overt retinal degeneration. Here, we provide direct and indirect mechanisms for the effect of CEP on macrophages, and show for the first time that antigen-specific T cells play a leading role in AMD pathogenesis. In vitro, CEP directly induced M1 macrophage polarization and production of M1-related factors by retinal pigment epithelial (RPE) cells. In vivo, CEP eye injections in mice induced acute pro-inflammatory gene expression in the retina and human AMD eyes showed distinctively diffuse CEP immunolabeling within RPE cells. Importantly, interferon-gamma (IFN-γ) and interleukin-17 (IL-17)-producing CEP-specific T cells were identified ex vivo after CEP immunization and promoted M1 polarization in co-culture experiments. Finally, T cell immunosuppressive therapy inhibited CEP-mediated pathology. These data indicate that T cells and M1 macrophages activated by oxidative damage cooperate in AMD pathogenesis. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cruz-Guilloty</LastName><ForeName>Fernando</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America ; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saeed</LastName><ForeName>Ali M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Duffort</LastName><ForeName>Stephanie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cano</LastName><ForeName>Marisol</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ebrahimi</LastName><ForeName>Katayoon B</ForeName><Initials>KB</Initials><AffiliationInfo><Affiliation>Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ballmick</LastName><ForeName>Asha</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Yaohong</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Hua</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Laird</LastName><ForeName>James M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Salomon</LastName><ForeName>Robert G</ForeName><Initials>RG</Initials><AffiliationInfo><Affiliation>Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Handa</LastName><ForeName>James T</ForeName><Initials>JT</Initials><AffiliationInfo><Affiliation>Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perez</LastName><ForeName>Victor L</ForeName><Initials>VL</Initials><AffiliationInfo><Affiliation>Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America ; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 EY019904</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 EY014801</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>EY14005</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 EY014005</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 EY016813</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><Agency>Howard Hughes Medical Institute</Agency><Country>United States</Country></Grant><Grant><GrantID>P30EY14801</GrantID><Acronym>EY</Acronym><Agency>NEI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01-GM21249</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>EY019904</GrantID><Acronym>EY</Acronym><Agency>NEI 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>2014</Year><Month>02</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015851">Interleukin-7</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011758">Pyrroles</NameOfSubstance></Chemical><Chemical><RegistryNumber>82115-62-6</RegistryNumber><NameOfSubstance UI="D007371">Interferon-gamma</NameOfSubstance></Chemical><Chemical><RegistryNumber>83HN0GTJ6D</RegistryNumber><NameOfSubstance UI="D016572">Cyclosporine</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="D001692" MajorTopicYN="N">Biological Transport</DescriptorName><QualifierName 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