Characterization of the thymic IL-7 niche in vivo
Identifieur interne : 002849 ( Pmc/Checkpoint ); précédent : 002848; suivant : 002850Characterization of the thymic IL-7 niche in vivo
Auteurs : Nuno L. Alves [France] ; Odile Richard-Le Goff [France] ; Nicholas D. Huntington [France] ; Ana Patricia Sousa [France] ; Vera S. G. Ribeiro [France] ; Allison Bordack [France] ; Francina Langa Vives ; Lucie Peduto [France] ; Ann Chidgey [Australie] ; Ana Cumano [France] ; Richard Boyd [Australie] ; Gerard Eberl [France] ; James P. Di Santo [France]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2009.
Abstract
The thymus represents the “cradle” for T cell development, with thymic stroma providing multiple soluble and membrane cues to developing thymocytes. Although IL-7 is recognized as an essential factor for thymopoiesis, the “environmental niche” of thymic IL-7 activity remains poorly characterized in vivo. Using bacterial artificial chromosome transgenic mice in which YFP is under control of IL-7 promoter, we identify a subset of thymic epithelial cells (TECs) that co-express YFP and high levels of
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DOI: 10.1073/pnas.0809559106
PubMed: 19164539
PubMed Central: 2635771
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Alves</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Goff, Odile Richard Le" sort="Goff, Odile Richard Le" uniqKey="Goff O" first="Odile Richard-Le" last="Goff">Odile Richard-Le Goff</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D." last="Huntington">Nicholas D. 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G." last="Ribeiro">Vera S. G. Ribeiro</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bordack, Allison" sort="Bordack, Allison" uniqKey="Bordack A" first="Allison" last="Bordack">Allison Bordack</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vives, Francina Langa" sort="Vives, Francina Langa" uniqKey="Vives F" first="Francina Langa" last="Vives">Francina Langa Vives</name><affiliation><nlm:aff wicri:cut=", and" id="aff3">Plate-Forme Technologique Centre d'Ingénierie Génétique Murine</nlm:aff></affiliation></author><author><name sortKey="Peduto, Lucie" sort="Peduto, Lucie" uniqKey="Peduto L" first="Lucie" last="Peduto">Lucie Peduto</name><affiliation wicri:level="3"><nlm:aff id="aff4">Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Chidgey, Ann" sort="Chidgey, Ann" uniqKey="Chidgey A" first="Ann" last="Chidgey">Ann Chidgey</name><affiliation wicri:level="1"><nlm:aff id="aff6">Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Victoria 3800, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Cumano, Ana" sort="Cumano, Ana" uniqKey="Cumano A" first="Ana" last="Cumano">Ana Cumano</name><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation><nlm:aff id="aff2">Lymphocyte Development Unit,</nlm:aff></affiliation></author><author><name sortKey="Boyd, Richard" sort="Boyd, Richard" uniqKey="Boyd R" first="Richard" last="Boyd">Richard Boyd</name><affiliation wicri:level="1"><nlm:aff id="aff6">Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Victoria 3800, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Eberl, Gerard" sort="Eberl, Gerard" uniqKey="Eberl G" first="Gerard" last="Eberl">Gerard Eberl</name><affiliation wicri:level="3"><nlm:aff id="aff4">Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Di Santo, James P" sort="Di Santo, James P" uniqKey="Di Santo J" first="James P." last="Di Santo">James P. Di Santo</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19164539</idno><idno type="pmc">2635771</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635771</idno><idno type="RBID">PMC:2635771</idno><idno type="doi">10.1073/pnas.0809559106</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">001B20</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001B20</idno><idno type="wicri:Area/Pmc/Curation">001978</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001978</idno><idno type="wicri:Area/Pmc/Checkpoint">002849</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002849</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Characterization of the thymic IL-7 niche in vivo</title><author><name sortKey="Alves, Nuno L" sort="Alves, Nuno L" uniqKey="Alves N" first="Nuno L." last="Alves">Nuno L. Alves</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Goff, Odile Richard Le" sort="Goff, Odile Richard Le" uniqKey="Goff O" first="Odile Richard-Le" last="Goff">Odile Richard-Le Goff</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D." last="Huntington">Nicholas D. Huntington</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Sousa, Ana Patricia" sort="Sousa, Ana Patricia" uniqKey="Sousa A" first="Ana Patricia" last="Sousa">Ana Patricia Sousa</name><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation><nlm:aff id="aff2">Lymphocyte Development Unit,</nlm:aff></affiliation></author><author><name sortKey="Ribeiro, Vera S G" sort="Ribeiro, Vera S G" uniqKey="Ribeiro V" first="Vera S. G." last="Ribeiro">Vera S. G. Ribeiro</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bordack, Allison" sort="Bordack, Allison" uniqKey="Bordack A" first="Allison" last="Bordack">Allison Bordack</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vives, Francina Langa" sort="Vives, Francina Langa" uniqKey="Vives F" first="Francina Langa" last="Vives">Francina Langa Vives</name><affiliation><nlm:aff wicri:cut=", and" id="aff3">Plate-Forme Technologique Centre d'Ingénierie Génétique Murine</nlm:aff></affiliation></author><author><name sortKey="Peduto, Lucie" sort="Peduto, Lucie" uniqKey="Peduto L" first="Lucie" last="Peduto">Lucie Peduto</name><affiliation wicri:level="3"><nlm:aff id="aff4">Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Chidgey, Ann" sort="Chidgey, Ann" uniqKey="Chidgey A" first="Ann" last="Chidgey">Ann Chidgey</name><affiliation wicri:level="1"><nlm:aff id="aff6">Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Victoria 3800, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Cumano, Ana" sort="Cumano, Ana" uniqKey="Cumano A" first="Ana" last="Cumano">Ana Cumano</name><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation><nlm:aff id="aff2">Lymphocyte Development Unit,</nlm:aff></affiliation></author><author><name sortKey="Boyd, Richard" sort="Boyd, Richard" uniqKey="Boyd R" first="Richard" last="Boyd">Richard Boyd</name><affiliation wicri:level="1"><nlm:aff id="aff6">Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Victoria 3800, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Eberl, Gerard" sort="Eberl, Gerard" uniqKey="Eberl G" first="Gerard" last="Eberl">Gerard Eberl</name><affiliation wicri:level="3"><nlm:aff id="aff4">Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Di Santo, James P" sort="Di Santo, James P" uniqKey="Di Santo J" first="James P." last="Di Santo">James P. Di Santo</name><affiliation><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit,</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff5">INSERM U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The thymus represents the “cradle” for T cell development, with thymic stroma providing multiple soluble and membrane cues to developing thymocytes. Although IL-7 is recognized as an essential factor for thymopoiesis, the “environmental niche” of thymic IL-7 activity remains poorly characterized in vivo. Using bacterial artificial chromosome transgenic mice in which YFP is under control of IL-7 promoter, we identify a subset of thymic epithelial cells (TECs) that co-express YFP and high levels of <italic>Il7</italic> transcripts (IL-7<sup>hi</sup> cells). IL-7<sup>hi</sup> TECs arise during early fetal development, persist throughout life, and co-express homeostatic chemokines (<italic>Ccl19</italic>, <italic>Ccl25</italic>, <italic>Cxcl12</italic>) and cytokines (<italic>Il15</italic>) that are critical for normal thymopoiesis. In the adult thymus, IL-7<sup>hi</sup> cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7<sup>hi</sup> cells decreases with age, suggesting a mechanism for the age-related thymic involution that is associated with declining IL-7 levels. Our temporal-spatial analysis of IL-7-producing cells in the thymus in vivo suggests that thymic IL-7 levels are dynamically regulated under distinct physiological conditions. This IL-7 reporter mouse provides a valuable tool to further dissect the mechanisms that govern thymic IL-7 expression in vivo.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19164539</article-id><article-id pub-id-type="pmc">2635771</article-id><article-id pub-id-type="publisher-id">6374</article-id><article-id pub-id-type="doi">10.1073/pnas.0809559106</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Immunology</subject></subj-group></subj-group></article-categories><title-group><article-title>Characterization of the thymic IL-7 niche in vivo</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Alves</surname><given-names>Nuno L.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff5"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Goff</surname><given-names>Odile Richard-Le</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff5"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Huntington</surname><given-names>Nicholas D.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff5"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sousa</surname><given-names>Ana Patricia</given-names></name><xref ref-type="aff" rid="aff5"><sup>b</sup></xref><xref ref-type="aff" rid="aff2"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ribeiro</surname><given-names>Vera S. G.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff5"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bordack</surname><given-names>Allison</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff5"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vives</surname><given-names>Francina Langa</given-names></name><xref ref-type="aff" rid="aff3"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Peduto</surname><given-names>Lucie</given-names></name><xref ref-type="aff" rid="aff4"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chidgey</surname><given-names>Ann</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cumano</surname><given-names>Ana</given-names></name><xref ref-type="aff" rid="aff5"><sup>b</sup></xref><xref ref-type="aff" rid="aff2"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Boyd</surname><given-names>Richard</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Eberl</surname><given-names>Gerard</given-names></name><xref ref-type="aff" rid="aff4"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Di Santo</surname><given-names>James P.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff5"><sup>b</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1"><sup>a</sup>Cytokines and Lymphoid Development Unit,</aff><aff id="aff2"><sup>c</sup>Lymphocyte Development Unit,</aff><aff id="aff3"><sup>d</sup>Plate-Forme Technologique Centre d'Ingénierie Génétique Murine, and</aff><aff id="aff4"><sup>e</sup>Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris, France;</aff><aff id="aff5"><sup>b</sup>INSERM U668, Paris, France; and</aff><aff id="aff6"><sup>f</sup>Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Victoria 3800, Australia</aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence should be addressed. E-mail: <email>disanto@pasteur.fr</email></corresp><fn fn-type="edited-by"><p>Edited by Max D. Cooper, Emory University, Atlanta, GA, and approved December 2, 2008</p></fn><fn fn-type="con"><p>Author contributions: N.L.A. and J.P.D. designed research; N.L.A., O.R.-L.G., N.D.H., A.P.S., V.S.G.R., A.B., F.L.V., L.P., A. Chidgey, and A. Cumano performed research; R.B. and G.E. contributed new reagents/analytic tools; N.L.A., N.D.H., and A. Chidgey analyzed data; and N.L.A. and J.P.D. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>3</day><month>2</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>21</day><month>1</month><year>2009</year></pub-date><volume>106</volume><issue>5</issue><fpage>1512</fpage><lpage>1517</lpage><history><date date-type="received"><day>25</day><month>9</month><year>2008</year></date></history><permissions><copyright-statement>© 2009 by The National Academy of Sciences of the USA</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq00509001512.pdf"></self-uri><abstract><p>The thymus represents the “cradle” for T cell development, with thymic stroma providing multiple soluble and membrane cues to developing thymocytes. Although IL-7 is recognized as an essential factor for thymopoiesis, the “environmental niche” of thymic IL-7 activity remains poorly characterized in vivo. Using bacterial artificial chromosome transgenic mice in which YFP is under control of IL-7 promoter, we identify a subset of thymic epithelial cells (TECs) that co-express YFP and high levels of <italic>Il7</italic> transcripts (IL-7<sup>hi</sup> cells). IL-7<sup>hi</sup> TECs arise during early fetal development, persist throughout life, and co-express homeostatic chemokines (<italic>Ccl19</italic>, <italic>Ccl25</italic>, <italic>Cxcl12</italic>) and cytokines (<italic>Il15</italic>) that are critical for normal thymopoiesis. In the adult thymus, IL-7<sup>hi</sup> cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7<sup>hi</sup> cells decreases with age, suggesting a mechanism for the age-related thymic involution that is associated with declining IL-7 levels. Our temporal-spatial analysis of IL-7-producing cells in the thymus in vivo suggests that thymic IL-7 levels are dynamically regulated under distinct physiological conditions. This IL-7 reporter mouse provides a valuable tool to further dissect the mechanisms that govern thymic IL-7 expression in vivo.</p></abstract><kwd-group><kwd>aging</kwd><kwd>development</kwd><kwd>thymic epithelial cells</kwd><kwd>thymus</kwd><kwd>cytokine</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Vives, Francina Langa" sort="Vives, Francina Langa" uniqKey="Vives F" first="Francina Langa" last="Vives">Francina Langa Vives</name></noCountry><country name="France"><region name="Île-de-France"><name sortKey="Alves, Nuno L" sort="Alves, Nuno L" uniqKey="Alves N" first="Nuno L." last="Alves">Nuno L. Alves</name></region><name sortKey="Bordack, Allison" sort="Bordack, Allison" uniqKey="Bordack A" first="Allison" last="Bordack">Allison Bordack</name><name sortKey="Cumano, Ana" sort="Cumano, Ana" uniqKey="Cumano A" first="Ana" last="Cumano">Ana Cumano</name><name sortKey="Di Santo, James P" sort="Di Santo, James P" uniqKey="Di Santo J" first="James P." last="Di Santo">James P. Di Santo</name><name sortKey="Eberl, Gerard" sort="Eberl, Gerard" uniqKey="Eberl G" first="Gerard" last="Eberl">Gerard Eberl</name><name sortKey="Goff, Odile Richard Le" sort="Goff, Odile Richard Le" uniqKey="Goff O" first="Odile Richard-Le" last="Goff">Odile Richard-Le Goff</name><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D." last="Huntington">Nicholas D. Huntington</name><name sortKey="Peduto, Lucie" sort="Peduto, Lucie" uniqKey="Peduto L" first="Lucie" last="Peduto">Lucie Peduto</name><name sortKey="Ribeiro, Vera S G" sort="Ribeiro, Vera S G" uniqKey="Ribeiro V" first="Vera S. G." last="Ribeiro">Vera S. G. Ribeiro</name><name sortKey="Sousa, Ana Patricia" sort="Sousa, Ana Patricia" uniqKey="Sousa A" first="Ana Patricia" last="Sousa">Ana Patricia Sousa</name></country><country name="Australie"><noRegion><name sortKey="Chidgey, Ann" sort="Chidgey, Ann" uniqKey="Chidgey A" first="Ann" last="Chidgey">Ann Chidgey</name></noRegion><name sortKey="Boyd, Richard" sort="Boyd, Richard" uniqKey="Boyd R" first="Richard" last="Boyd">Richard Boyd</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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