Serveur d'exploration sur le lymphœdème

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CLEC-2 is required for development and maintenance of lymph nodes

Identifieur interne : 001D02 ( Pmc/Checkpoint ); précédent : 001D01; suivant : 001D03

CLEC-2 is required for development and maintenance of lymph nodes

Auteurs : Cécile Bénézech ; Saba Nayar ; Brenda A. Finney [Royaume-Uni] ; David R. Withers ; Kate Lowe [Royaume-Uni] ; Guillaume E. Desanti ; Clare L. Marriott ; Steve P. Watson [Royaume-Uni] ; Jorge H. Caama O ; Christopher D. Buckley ; Francesca Barone

Source :

RBID : PMC:4023425

Abstract

Key Points

CLEC-2 is necessary for lymphatic cell proliferation and lymph node anlage persistence after birth.

Lack of CLEC-2 expression on megakaryocytes and platelets compromises lymph node integrity in adult life.


Url:
DOI: 10.1182/blood-2013-03-489286
PubMed: 24532804
PubMed Central: 4023425


Affiliations:


Links toward previous steps (curation, corpus...)


Links to Exploration step

PMC:4023425

Le document en format XML

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<list-item>
<p>CLEC-2 is necessary for lymphatic cell proliferation and lymph node anlage persistence after birth.</p>
</list-item>
<list-item>
<p>Lack of CLEC-2 expression on megakaryocytes and platelets compromises lymph node integrity in adult life.</p>
</list-item>
</list>
</p>
</div>
</front>
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<journal-id journal-id-type="iso-abbrev">Blood</journal-id>
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<journal-id journal-id-type="pmc">blood</journal-id>
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<title-group>
<article-title>CLEC-2 is required for development and maintenance of lymph nodes</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Bénézech</surname>
<given-names>Cécile</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nayar</surname>
<given-names>Saba</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Finney</surname>
<given-names>Brenda A.</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Withers</surname>
<given-names>David R.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lowe</surname>
<given-names>Kate</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Desanti</surname>
<given-names>Guillaume E.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Marriott</surname>
<given-names>Clare L.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Watson</surname>
<given-names>Steve P.</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Caamaño</surname>
<given-names>Jorge H.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Buckley</surname>
<given-names>Christopher D.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Barone</surname>
<given-names>Francesca</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<aff id="aff1">
<label>1</label>
School of Immunity and Infection and</aff>
<aff id="aff2">
<label>2</label>
Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom</aff>
</contrib-group>
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<month>5</month>
<year>2014</year>
</pub-date>
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<month>2</month>
<year>2014</year>
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<month>5</month>
<year>2014</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>123</volume>
<issue>20</issue>
<fpage>3200</fpage>
<lpage>3207</lpage>
<history>
<date date-type="received">
<day>12</day>
<month>3</month>
<year>2013</year>
</date>
<date date-type="accepted">
<day>24</day>
<month>1</month>
<year>2014</year>
</date>
</history>
<permissions>
<copyright-statement>© 2014 by The American Society of Hematology</copyright-statement>
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<abstract abstract-type="executive-summary">
<title>Key Points</title>
<p>
<list list-type="bullet">
<list-item>
<p>CLEC-2 is necessary for lymphatic cell proliferation and lymph node anlage persistence after birth.</p>
</list-item>
<list-item>
<p>Lack of CLEC-2 expression on megakaryocytes and platelets compromises lymph node integrity in adult life.</p>
</list-item>
</list>
</p>
</abstract>
<abstract>
<p>The importance of CLEC-2, a natural ligand/receptor for Gp38/Podoplanin, in the formation of the lymphatic vasculature has recently been demonstrated. As the development and maintenance of lymph nodes (LNs) is dependent on the formation of the lymphatic vasculature and the differentiation of Gp38/Podoplanin
<sup>+</sup>
stromal cells, we investigated the role of CLEC-2 in lymphoneogenesis and LN homeostasis. Using constitutive
<italic>Clec1b</italic>
<sup>
<italic>−/−</italic>
</sup>
mice, we showed that while CLEC-2 was not necessary for initiation of the LN anlage, it was required at late stages of development. Constitutive deletion of CLEC-2 induced a profound defect in lymphatic endothelial cell proliferation, resulting in lack of LNs at birth. In contrast, conditional deletion of CLEC-2 in the megakaryocyte/platelet lineage in
<italic>Clec1b
<sup>fl/fl</sup>
PF4-Cre</italic>
mice led to the development of blood-filled LNs and fibrosis, in absence of a proliferative defect of the lymphatic endothelial compartment. This phenotype was also observed in chimeric mice reconstituted with
<italic>Clec1b
<sup>fl/fl</sup>
PF4-Cre</italic>
bone marrow, indicating that CLEC-2 expression in platelets was required for LN integrity. We demonstrated that LNs of
<italic>Clec1b
<sup>fl/fl</sup>
PF4-Cre</italic>
mice are able to sustain primary immune responses but show a defect in immune cell recirculation after repeated immunizations, thus suggesting CLEC-2 as target in chronic immune response.</p>
</abstract>
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<affiliations>
<list>
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</country>
<region>
<li>Angleterre</li>
<li>Midlands de l'Ouest</li>
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<tree>
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<name sortKey="Barone, Francesca" sort="Barone, Francesca" uniqKey="Barone F" first="Francesca" last="Barone">Francesca Barone</name>
<name sortKey="Benezech, Cecile" sort="Benezech, Cecile" uniqKey="Benezech C" first="Cécile" last="Bénézech">Cécile Bénézech</name>
<name sortKey="Buckley, Christopher D" sort="Buckley, Christopher D" uniqKey="Buckley C" first="Christopher D." last="Buckley">Christopher D. Buckley</name>
<name sortKey="Caama O, Jorge H" sort="Caama O, Jorge H" uniqKey="Caama O J" first="Jorge H." last="Caama O">Jorge H. Caama O</name>
<name sortKey="Desanti, Guillaume E" sort="Desanti, Guillaume E" uniqKey="Desanti G" first="Guillaume E." last="Desanti">Guillaume E. Desanti</name>
<name sortKey="Marriott, Clare L" sort="Marriott, Clare L" uniqKey="Marriott C" first="Clare L." last="Marriott">Clare L. Marriott</name>
<name sortKey="Nayar, Saba" sort="Nayar, Saba" uniqKey="Nayar S" first="Saba" last="Nayar">Saba Nayar</name>
<name sortKey="Withers, David R" sort="Withers, David R" uniqKey="Withers D" first="David R." last="Withers">David R. Withers</name>
</noCountry>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Finney, Brenda A" sort="Finney, Brenda A" uniqKey="Finney B" first="Brenda A." last="Finney">Brenda A. Finney</name>
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<name sortKey="Lowe, Kate" sort="Lowe, Kate" uniqKey="Lowe K" first="Kate" last="Lowe">Kate Lowe</name>
<name sortKey="Watson, Steve P" sort="Watson, Steve P" uniqKey="Watson S" first="Steve P." last="Watson">Steve P. Watson</name>
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