Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice
Identifieur interne : 000196 ( Pmc/Checkpoint ); précédent : 000195; suivant : 000197Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice
Auteurs : Liang Gao ; David Brenner ; Enric Llorens-Bobadilla ; Gonzalo Saiz-Castro ; Tobias Frank ; Peter Wieghofer ; Oliver Hill ; Meinolf Thiemann ; Saoussen Karray ; Marco Prinz ; Jochen H. Weishaupt ; Ana Martin-VillalbaSource :
- The Journal of Experimental Medicine [ 0022-1007 ] ; 2015.
Abstract
Gao et al. report that genetic or pharmacological blockade of CD95 ligand prevents infiltration of peripheral myeloid cells and thereby averts toxin-induced neurodegeneration in mice.
Url:
DOI: 10.1084/jem.20132423
PubMed: 25779632
PubMed Central: 4387281
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice</title><author><name sortKey="Gao, Liang" sort="Gao, Liang" uniqKey="Gao L" first="Liang" last="Gao">Liang Gao</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Brenner, David" sort="Brenner, David" uniqKey="Brenner D" first="David" last="Brenner">David Brenner</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Llorens Bobadilla, Enric" sort="Llorens Bobadilla, Enric" uniqKey="Llorens Bobadilla E" first="Enric" last="Llorens-Bobadilla">Enric Llorens-Bobadilla</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Saiz Castro, Gonzalo" sort="Saiz Castro, Gonzalo" uniqKey="Saiz Castro G" first="Gonzalo" last="Saiz-Castro">Gonzalo Saiz-Castro</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Frank, Tobias" sort="Frank, Tobias" uniqKey="Frank T" first="Tobias" last="Frank">Tobias Frank</name><affiliation><nlm:aff id="aff2"><institution>Department of Neurology, University Medical Center, Georg-August-University, 37075 Göttingen, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Wieghofer, Peter" sort="Wieghofer, Peter" uniqKey="Wieghofer P" first="Peter" last="Wieghofer">Peter Wieghofer</name><affiliation><nlm:aff id="aff3"><institution>Institute of Neuropathology</institution>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff3"><institution>Faculty of Biology</institution></nlm:aff></affiliation></author><author><name sortKey="Hill, Oliver" sort="Hill, Oliver" uniqKey="Hill O" first="Oliver" last="Hill">Oliver Hill</name><affiliation><nlm:aff id="aff4"><institution>Apogenix GmbH, 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Thiemann, Meinolf" sort="Thiemann, Meinolf" uniqKey="Thiemann M" first="Meinolf" last="Thiemann">Meinolf Thiemann</name><affiliation><nlm:aff id="aff4"><institution>Apogenix GmbH, 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Karray, Saoussen" sort="Karray, Saoussen" uniqKey="Karray S" first="Saoussen" last="Karray">Saoussen Karray</name><affiliation><nlm:aff id="aff5"><institution>Institut National de la Santé et de la Recherche Médicale (INSERM), U1160, Université Paris Diderot, 75010 Paris, France</institution></nlm:aff></affiliation></author><author><name sortKey="Prinz, Marco" sort="Prinz, Marco" uniqKey="Prinz M" first="Marco" last="Prinz">Marco Prinz</name><affiliation><nlm:aff id="aff3"><institution>Institute of Neuropathology</institution>,</nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79098 Freiburg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Weishaupt, Jochen H" sort="Weishaupt, Jochen H" uniqKey="Weishaupt J" first="Jochen H." last="Weishaupt">Jochen H. Weishaupt</name><affiliation><nlm:aff id="aff6"><institution>Department of Neurology, University of Ulm, 89081 Ulm, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Martin Villalba, Ana" sort="Martin Villalba, Ana" uniqKey="Martin Villalba A" first="Ana" last="Martin-Villalba">Ana Martin-Villalba</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25779632</idno><idno type="pmc">4387281</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387281</idno><idno type="RBID">PMC:4387281</idno><idno type="doi">10.1084/jem.20132423</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000768</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000768</idno><idno type="wicri:Area/Pmc/Curation">000765</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000765</idno><idno type="wicri:Area/Pmc/Checkpoint">000196</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000196</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice</title><author><name sortKey="Gao, Liang" sort="Gao, Liang" uniqKey="Gao L" first="Liang" last="Gao">Liang Gao</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Brenner, David" sort="Brenner, David" uniqKey="Brenner D" first="David" last="Brenner">David Brenner</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Llorens Bobadilla, Enric" sort="Llorens Bobadilla, Enric" uniqKey="Llorens Bobadilla E" first="Enric" last="Llorens-Bobadilla">Enric Llorens-Bobadilla</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Saiz Castro, Gonzalo" sort="Saiz Castro, Gonzalo" uniqKey="Saiz Castro G" first="Gonzalo" last="Saiz-Castro">Gonzalo Saiz-Castro</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Frank, Tobias" sort="Frank, Tobias" uniqKey="Frank T" first="Tobias" last="Frank">Tobias Frank</name><affiliation><nlm:aff id="aff2"><institution>Department of Neurology, University Medical Center, Georg-August-University, 37075 Göttingen, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Wieghofer, Peter" sort="Wieghofer, Peter" uniqKey="Wieghofer P" first="Peter" last="Wieghofer">Peter Wieghofer</name><affiliation><nlm:aff id="aff3"><institution>Institute of Neuropathology</institution>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff3"><institution>Faculty of Biology</institution></nlm:aff></affiliation></author><author><name sortKey="Hill, Oliver" sort="Hill, Oliver" uniqKey="Hill O" first="Oliver" last="Hill">Oliver Hill</name><affiliation><nlm:aff id="aff4"><institution>Apogenix GmbH, 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Thiemann, Meinolf" sort="Thiemann, Meinolf" uniqKey="Thiemann M" first="Meinolf" last="Thiemann">Meinolf Thiemann</name><affiliation><nlm:aff id="aff4"><institution>Apogenix GmbH, 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Karray, Saoussen" sort="Karray, Saoussen" uniqKey="Karray S" first="Saoussen" last="Karray">Saoussen Karray</name><affiliation><nlm:aff id="aff5"><institution>Institut National de la Santé et de la Recherche Médicale (INSERM), U1160, Université Paris Diderot, 75010 Paris, France</institution></nlm:aff></affiliation></author><author><name sortKey="Prinz, Marco" sort="Prinz, Marco" uniqKey="Prinz M" first="Marco" last="Prinz">Marco Prinz</name><affiliation><nlm:aff id="aff3"><institution>Institute of Neuropathology</institution>,</nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79098 Freiburg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Weishaupt, Jochen H" sort="Weishaupt, Jochen H" uniqKey="Weishaupt J" first="Jochen H." last="Weishaupt">Jochen H. Weishaupt</name><affiliation><nlm:aff id="aff6"><institution>Department of Neurology, University of Ulm, 89081 Ulm, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Martin Villalba, Ana" sort="Martin Villalba, Ana" uniqKey="Martin Villalba A" first="Ana" last="Martin-Villalba">Ana Martin-Villalba</name><affiliation><nlm:aff id="aff1"><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Experimental Medicine</title><idno type="ISSN">0022-1007</idno><idno type="eISSN">1540-9538</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Gao et al. report that genetic or pharmacological blockade of CD95 ligand prevents infiltration of peripheral myeloid cells and thereby averts toxin-induced neurodegeneration in mice.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Adachi, M" uniqKey="Adachi M">M. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Exp Med</journal-id><journal-id journal-id-type="iso-abbrev">J. Exp. Med</journal-id><journal-id journal-id-type="hwp">jem</journal-id><journal-id journal-id-type="publisher-id">jem</journal-id><journal-title-group><journal-title>The Journal of Experimental Medicine</journal-title></journal-title-group><issn pub-type="ppub">0022-1007</issn><issn pub-type="epub">1540-9538</issn><publisher><publisher-name>The Rockefeller University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25779632</article-id><article-id pub-id-type="pmc">4387281</article-id><article-id pub-id-type="publisher-id">20132423</article-id><article-id pub-id-type="doi">10.1084/jem.20132423</article-id><article-categories><subj-group subj-group-type="heading"><subject>Brief Definitive Report</subject></subj-group></article-categories><title-group><article-title>Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice</article-title><alt-title alt-title-type="short">Monocyte infiltration in neurodegeneration by CD95</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gao</surname><given-names>Liang</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Brenner</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Llorens-Bobadilla</surname><given-names>Enric</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Saiz-Castro</surname><given-names>Gonzalo</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Frank</surname><given-names>Tobias</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wieghofer</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff3">4</xref></contrib><contrib contrib-type="author"><name><surname>Hill</surname><given-names>Oliver</given-names></name><xref ref-type="aff" rid="aff4">6</xref></contrib><contrib contrib-type="author"><name><surname>Thiemann</surname><given-names>Meinolf</given-names></name><xref ref-type="aff" rid="aff4">6</xref></contrib><contrib contrib-type="author"><name><surname>Karray</surname><given-names>Saoussen</given-names></name><xref ref-type="aff" rid="aff5">7</xref></contrib><contrib contrib-type="author"><name><surname>Prinz</surname><given-names>Marco</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff3">5</xref></contrib><contrib contrib-type="author"><name><surname>Weishaupt</surname><given-names>Jochen H.</given-names></name><xref ref-type="aff" rid="aff6">8</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Martin-Villalba</surname><given-names>Ana</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib></contrib-group><aff id="aff1"><label>1</label><institution>Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany</institution></aff><aff id="aff2"><label>2</label><institution>Department of Neurology, University Medical Center, Georg-August-University, 37075 Göttingen, Germany</institution></aff><aff id="aff3"><label>3</label><institution>Institute of Neuropathology</institution>,<label>4</label><institution>Faculty of Biology</institution>, and<label>5</label><institution>BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79098 Freiburg, Germany</institution></aff><aff id="aff4"><label>6</label><institution>Apogenix GmbH, 69120 Heidelberg, Germany</institution></aff><aff id="aff5"><label>7</label><institution>Institut National de la Santé et de la Recherche Médicale (INSERM), U1160, Université Paris Diderot, 75010 Paris, France</institution></aff><aff id="aff6"><label>8</label><institution>Department of Neurology, University of Ulm, 89081 Ulm, Germany</institution></aff><author-notes><corresp>CORRESPONDENCE Ana Martin-Villalba: <email>a.martin-villalba@dkfz.de</email></corresp><fn id="fn1"><label>*</label><p>L. Gao and D. Brenner contributed equally to this paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>6</day><month>4</month><year>2015</year></pub-date><volume>212</volume><issue>4</issue><fpage>469</fpage><lpage>480</lpage><history><date date-type="received"><day>21</day><month>11</month><year>2013</year></date><date date-type="accepted"><day>26</day><month>2</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 Gao et al.</copyright-statement><copyright-year>2015</copyright-year><license license-type="openaccess"><license-p>This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see <ext-link ext-link-type="uri" xlink:href="http://www.rupress.org/terms">http://www.rupress.org/terms</ext-link>). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0/">http://creativecommons.org/licenses/by-nc-sa/3.0/</ext-link>).</license-p></license></permissions><self-uri xlink:role="icon" xlink:href="JEM_20132423_thumb.gif"></self-uri><abstract abstract-type="precis"><p>Gao et al. report that genetic or pharmacological blockade of CD95 ligand prevents infiltration of peripheral myeloid cells and thereby averts toxin-induced neurodegeneration in mice.</p></abstract><abstract><p>Neuroinflammation is increasingly recognized as a hallmark of neurodegeneration. Activated central nervous system–resident microglia and infiltrating immune cells contribute to the degeneration of dopaminergic neurons (DNs). However, how the inflammatory process leads to neuron loss and whether blocking this response would be beneficial to disease progression remains largely unknown. CD95 is a mediator of inflammation that has also been proposed as an apoptosis inducer in DNs, but previous studies using ubiquitous deletion of CD95 or CD95L in mouse models of neurodegeneration have generated conflicting results. Here we examine the role of CD95 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)–induced neurodegeneration using tissue-specific deletion of CD95 or CD95L. We show that DN death is not mediated by CD95-induced apoptosis because deletion of CD95 in DNs does not influence MPTP-induced neurodegeneration. In contrast, deletion of CD95L in peripheral myeloid cells significantly protects against MPTP neurotoxicity and preserves striatal dopamine levels. Systemic pharmacological inhibition of CD95L dampens the peripheral innate response, reduces the accumulation of infiltrating myeloid cells, and efficiently prevents MPTP-induced DN death. Altogether, this study emphasizes the role of the peripheral innate immune response in neurodegeneration and identifies CD95 as potential pharmacological target for neurodegenerative disease.</p></abstract></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Brenner, David" sort="Brenner, David" uniqKey="Brenner D" first="David" last="Brenner">David Brenner</name><name sortKey="Frank, Tobias" sort="Frank, Tobias" uniqKey="Frank T" first="Tobias" last="Frank">Tobias Frank</name><name sortKey="Gao, Liang" sort="Gao, Liang" uniqKey="Gao L" first="Liang" last="Gao">Liang Gao</name><name sortKey="Hill, Oliver" sort="Hill, Oliver" uniqKey="Hill O" first="Oliver" last="Hill">Oliver Hill</name><name sortKey="Karray, Saoussen" sort="Karray, Saoussen" uniqKey="Karray S" first="Saoussen" last="Karray">Saoussen Karray</name><name sortKey="Llorens Bobadilla, Enric" sort="Llorens Bobadilla, Enric" uniqKey="Llorens Bobadilla E" first="Enric" last="Llorens-Bobadilla">Enric Llorens-Bobadilla</name><name sortKey="Martin Villalba, Ana" sort="Martin Villalba, Ana" uniqKey="Martin Villalba A" first="Ana" last="Martin-Villalba">Ana Martin-Villalba</name><name sortKey="Prinz, Marco" sort="Prinz, Marco" uniqKey="Prinz M" first="Marco" last="Prinz">Marco Prinz</name><name sortKey="Saiz Castro, Gonzalo" sort="Saiz Castro, Gonzalo" uniqKey="Saiz Castro G" first="Gonzalo" last="Saiz-Castro">Gonzalo Saiz-Castro</name><name sortKey="Thiemann, Meinolf" sort="Thiemann, Meinolf" uniqKey="Thiemann M" first="Meinolf" last="Thiemann">Meinolf Thiemann</name><name sortKey="Weishaupt, Jochen H" sort="Weishaupt, Jochen H" uniqKey="Weishaupt J" first="Jochen H." last="Weishaupt">Jochen H. Weishaupt</name><name sortKey="Wieghofer, Peter" sort="Wieghofer, Peter" uniqKey="Wieghofer P" first="Peter" last="Wieghofer">Peter Wieghofer</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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