Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis
Identifieur interne : 000152 ( Pmc/Curation ); précédent : 000151; suivant : 000153Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis
Auteurs : Franziska Herster [Allemagne] ; Zsofia Bittner [Allemagne] ; Nathan K. Archer [États-Unis] ; Sabine Dickhöfer [Allemagne] ; David Eisel [Allemagne] ; Tatjana Eigenbrod [Allemagne] ; Thomas Knorpp [Allemagne] ; Nicole Schneiderhan-Marra [Allemagne] ; Markus W. Löffler [Allemagne] ; Hubert Kalbacher [Allemagne] ; Tim Vierbuchen [Allemagne] ; Holger Heine [Allemagne] ; Lloyd S. Miller [États-Unis] ; Dominik Hartl [Allemagne, Suisse] ; Lukas Freund [Allemagne] ; Knut Sch Kel [Allemagne] ; Martin Heister [Allemagne] ; Kamran Ghoreschi [Allemagne] ; Alexander N. R. Weber [Allemagne]Source :
- Nature Communications [ 2041-1723 ] ; 2020.
Abstract
Psoriasis is an inflammatory skin disease with strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37. LL37 in complex with DNA and RNA is thought to initiate disease exacerbation via plasmacytoid dendritic cells. However, the source of nucleic acids supposed to start this initial inflammatory event remains unknown. We show here that primary murine and human PMNs mount a fulminant and self-propagating neutrophil extracellular trap (NET) and cytokine response, but independently of the canonical NET component, DNA. Unexpectedly, RNA, which is abundant in NETs and psoriatic but not healthy skin, in complex with LL37 triggered TLR8/TLR13-mediated cytokine and NET release by PMNs in vitro and in vivo. Transfer of NETs to naive human PMNs prompts additional NET release, promoting further inflammation. Our study thus uncovers a self-propagating vicious cycle contributing to chronic inflammation in psoriasis, and NET-associated RNA (naRNA) as a physiologically relevant NET component.
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DOI: 10.1038/s41467-019-13756-4
PubMed: 31913271
PubMed Central: 6949246
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440, 69120 Heidelberg</wicri:regionArea></affiliation></author><author><name sortKey="Heister, Martin" sort="Heister, Martin" uniqKey="Heister M" first="Martin" last="Heister">Martin Heister</name><affiliation wicri:level="1"><nlm:aff id="Aff12"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0196 8249</institution-id><institution-id institution-id-type="GRID">grid.411544.1</institution-id><institution>Department of Dermatology,</institution><institution>University Hospital Tübingen,</institution></institution-wrap>Liebermeisterstr. 25, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Liebermeisterstr. 25, 72076 Tübingen</wicri:regionArea></affiliation></author><author><name sortKey="Ghoreschi, Kamran" sort="Ghoreschi, Kamran" uniqKey="Ghoreschi K" first="Kamran" last="Ghoreschi">Kamran Ghoreschi</name><affiliation wicri:level="1"><nlm:aff id="Aff12"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0196 8249</institution-id><institution-id institution-id-type="GRID">grid.411544.1</institution-id><institution>Department of Dermatology,</institution><institution>University Hospital Tübingen,</institution></institution-wrap>Liebermeisterstr. 25, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Liebermeisterstr. 25, 72076 Tübingen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff13"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2218 4662</institution-id><institution-id institution-id-type="GRID">grid.6363.0</institution-id><institution>Department of Dermatology, Charité – Universitätsmedizin Berlin,</institution></institution-wrap>Charitéplatz 1, 10117 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Charitéplatz 1, 10117 Berlin</wicri:regionArea></affiliation></author><author><name sortKey="Weber, Alexander N R" sort="Weber, Alexander N R" 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Weber</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Department of Immunology,</institution><institution>University of Tübingen,</institution></institution-wrap>Auf der Morgenstelle 15, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Auf der Morgenstelle 15, 72076 Tübingen</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31913271</idno><idno type="pmc">6949246</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949246</idno><idno type="RBID">PMC:6949246</idno><idno type="doi">10.1038/s41467-019-13756-4</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000152</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000152</idno><idno type="wicri:Area/Pmc/Curation">000152</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000152</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis</title><author><name sortKey="Herster, Franziska" sort="Herster, Franziska" uniqKey="Herster F" first="Franziska" last="Herster">Franziska Herster</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Department of Immunology,</institution><institution>University of Tübingen,</institution></institution-wrap>Auf der Morgenstelle 15, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Auf der Morgenstelle 15, 72076 Tübingen</wicri:regionArea></affiliation></author><author><name sortKey="Bittner, Zsofia" sort="Bittner, Zsofia" uniqKey="Bittner Z" first="Zsofia" last="Bittner">Zsofia Bittner</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Department of Immunology,</institution><institution>University of Tübingen,</institution></institution-wrap>Auf der Morgenstelle 15, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Auf der Morgenstelle 15, 72076 Tübingen</wicri:regionArea></affiliation></author><author><name sortKey="Archer, Nathan K" sort="Archer, Nathan K" uniqKey="Archer N" first="Nathan K." last="Archer">Nathan K. Archer</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2171 9311</institution-id><institution-id institution-id-type="GRID">grid.21107.35</institution-id><institution>Department of Dermatology,</institution><institution>Johns Hopkins University School of Medicine,</institution></institution-wrap>Baltimore, MD 21231 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Dickhofer, Sabine" sort="Dickhofer, Sabine" uniqKey="Dickhofer S" first="Sabine" last="Dickhöfer">Sabine Dickhöfer</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Department of Immunology,</institution><institution>University of Tübingen,</institution></institution-wrap>Auf der Morgenstelle 15, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Auf der Morgenstelle 15, 72076 Tübingen</wicri:regionArea></affiliation></author><author><name sortKey="Eisel, David" sort="Eisel, David" uniqKey="Eisel D" first="David" last="Eisel">David Eisel</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Department of Immunology,</institution><institution>University of Tübingen,</institution></institution-wrap>Auf der Morgenstelle 15, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Auf der Morgenstelle 15, 72076 Tübingen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff14"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 4692 2203</institution-id><institution-id institution-id-type="GRID">grid.434484.b</institution-id><institution>Present Address: David Eisel, BioNTech,</institution></institution-wrap>An der Goldgrube 12, 55131 Mainz, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>An der Goldgrube 12, 55131 Mainz</wicri:regionArea></affiliation></author><author><name sortKey="Eigenbrod, Tatjana" sort="Eigenbrod, Tatjana" uniqKey="Eigenbrod T" first="Tatjana" last="Eigenbrod">Tatjana Eigenbrod</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0328 4908</institution-id><institution-id institution-id-type="GRID">grid.5253.1</institution-id><institution>Department of Infectious Diseases, Medical Microbiology and Hygiene,</institution><institution>University Hospital Heidelberg,</institution></institution-wrap>Im Neuenheimer Feld 324, 69120 Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Im Neuenheimer Feld 324, 69120 Heidelberg</wicri:regionArea></affiliation></author><author><name sortKey="Knorpp, Thomas" sort="Knorpp, Thomas" uniqKey="Knorpp T" first="Thomas" last="Knorpp">Thomas Knorpp</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9457 1306</institution-id><institution-id institution-id-type="GRID">grid.461765.7</institution-id><institution>NMI Natural and Medical Sciences Institute at the University of Tübingen,</institution></institution-wrap>Markwiesenstr. 55, 72770 Reutlingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Markwiesenstr. 55, 72770 Reutlingen</wicri:regionArea></affiliation></author><author><name sortKey="Schneiderhan Marra, Nicole" sort="Schneiderhan Marra, Nicole" uniqKey="Schneiderhan Marra N" first="Nicole" last="Schneiderhan-Marra">Nicole Schneiderhan-Marra</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9457 1306</institution-id><institution-id institution-id-type="GRID">grid.461765.7</institution-id><institution>NMI Natural and Medical Sciences Institute at the University of Tübingen,</institution></institution-wrap>Markwiesenstr. 55, 72770 Reutlingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Markwiesenstr. 55, 72770 Reutlingen</wicri:regionArea></affiliation></author><author><name sortKey="Loffler, Markus W" sort="Loffler, Markus W" uniqKey="Loffler M" first="Markus W." last="Löffler">Markus W. Löffler</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Department of Immunology,</institution><institution>University of Tübingen,</institution></institution-wrap>Auf der Morgenstelle 15, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Auf der Morgenstelle 15, 72076 Tübingen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0196 8249</institution-id><institution-id institution-id-type="GRID">grid.411544.1</institution-id><institution>Department of General, Visceral and Transplant Surgery,</institution><institution>University Hospital Tübingen,</institution></institution-wrap>Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Hoppe-Seyler-Str. 3, 72076 Tübingen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0196 8249</institution-id><institution-id institution-id-type="GRID">grid.411544.1</institution-id><institution>Department of Clinical Pharmacology,</institution><institution>University Hospital Tübingen,</institution></institution-wrap>Auf der Morgenstelle 8, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Auf der Morgenstelle 8, 72076 Tübingen</wicri:regionArea></affiliation></author><author><name sortKey="Kalbacher, Hubert" sort="Kalbacher, Hubert" uniqKey="Kalbacher H" first="Hubert" last="Kalbacher">Hubert Kalbacher</name><affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Interfaculty Institute of Biochemistry, University of Tübingen,</institution></institution-wrap>Hoppe-Seyler-Str. 4, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Hoppe-Seyler-Str. 4, 72076 Tübingen</wicri:regionArea></affiliation></author><author><name sortKey="Vierbuchen, Tim" sort="Vierbuchen, Tim" uniqKey="Vierbuchen T" first="Tim" last="Vierbuchen">Tim Vierbuchen</name><affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0493 9170</institution-id><institution-id institution-id-type="GRID">grid.418187.3</institution-id><institution>Research Group Innate Immunity, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Deutsches Zentrum für Lungenforschung (DZL),</institution></institution-wrap>Parkallee 22, 23845 Borstel, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Parkallee 22, 23845 Borstel</wicri:regionArea></affiliation></author><author><name sortKey="Heine, Holger" sort="Heine, Holger" uniqKey="Heine H" first="Holger" last="Heine">Holger Heine</name><affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0493 9170</institution-id><institution-id institution-id-type="GRID">grid.418187.3</institution-id><institution>Research Group Innate Immunity, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Deutsches Zentrum für Lungenforschung (DZL),</institution></institution-wrap>Parkallee 22, 23845 Borstel, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Parkallee 22, 23845 Borstel</wicri:regionArea></affiliation></author><author><name sortKey="Miller, Lloyd S" sort="Miller, Lloyd S" uniqKey="Miller L" first="Lloyd S." last="Miller">Lloyd S. Miller</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2171 9311</institution-id><institution-id institution-id-type="GRID">grid.21107.35</institution-id><institution>Department of Dermatology,</institution><institution>Johns Hopkins University School of Medicine,</institution></institution-wrap>Baltimore, MD 21231 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Hartl, Dominik" sort="Hartl, Dominik" uniqKey="Hartl D" first="Dominik" last="Hartl">Dominik Hartl</name><affiliation wicri:level="1"><nlm:aff id="Aff9"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>University Children’s Hospital and Interdisciplinary Center for Infectious Diseases, University of Tübingen,</institution></institution-wrap>Hoppe-Seyler-Str. 1, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Hoppe-Seyler-Str. 1, 72076 Tübingen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 1515 9979</institution-id><institution-id institution-id-type="GRID">grid.419481.1</institution-id><institution>Novartis Institutes for BioMedical Research (NIBR),</institution></institution-wrap>Basel, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Basel</wicri:regionArea></affiliation></author><author><name sortKey="Freund, Lukas" sort="Freund, Lukas" uniqKey="Freund L" first="Lukas" last="Freund">Lukas Freund</name><affiliation wicri:level="1"><nlm:aff id="Aff11"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0328 4908</institution-id><institution-id institution-id-type="GRID">grid.5253.1</institution-id><institution>Department of Dermatology,</institution><institution>University Hospital Heidelberg,</institution></institution-wrap>Im Neuenheimer Feld 440, 69120 Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Im Neuenheimer Feld 440, 69120 Heidelberg</wicri:regionArea></affiliation></author><author><name sortKey="Sch Kel, Knut" sort="Sch Kel, Knut" uniqKey="Sch Kel K" first="Knut" last="Sch Kel">Knut Sch Kel</name><affiliation wicri:level="1"><nlm:aff id="Aff11"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0328 4908</institution-id><institution-id institution-id-type="GRID">grid.5253.1</institution-id><institution>Department of Dermatology,</institution><institution>University Hospital Heidelberg,</institution></institution-wrap>Im Neuenheimer Feld 440, 69120 Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Im Neuenheimer Feld 440, 69120 Heidelberg</wicri:regionArea></affiliation></author><author><name sortKey="Heister, Martin" sort="Heister, Martin" uniqKey="Heister M" first="Martin" last="Heister">Martin Heister</name><affiliation wicri:level="1"><nlm:aff id="Aff12"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0196 8249</institution-id><institution-id institution-id-type="GRID">grid.411544.1</institution-id><institution>Department of Dermatology,</institution><institution>University Hospital Tübingen,</institution></institution-wrap>Liebermeisterstr. 25, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Liebermeisterstr. 25, 72076 Tübingen</wicri:regionArea></affiliation></author><author><name sortKey="Ghoreschi, Kamran" sort="Ghoreschi, Kamran" uniqKey="Ghoreschi K" first="Kamran" last="Ghoreschi">Kamran Ghoreschi</name><affiliation wicri:level="1"><nlm:aff id="Aff12"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0196 8249</institution-id><institution-id institution-id-type="GRID">grid.411544.1</institution-id><institution>Department of Dermatology,</institution><institution>University Hospital Tübingen,</institution></institution-wrap>Liebermeisterstr. 25, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Liebermeisterstr. 25, 72076 Tübingen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff13"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2218 4662</institution-id><institution-id institution-id-type="GRID">grid.6363.0</institution-id><institution>Department of Dermatology, Charité – Universitätsmedizin Berlin,</institution></institution-wrap>Charitéplatz 1, 10117 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Charitéplatz 1, 10117 Berlin</wicri:regionArea></affiliation></author><author><name sortKey="Weber, Alexander N R" sort="Weber, Alexander N R" uniqKey="Weber A" first="Alexander N. R." last="Weber">Alexander N. R. Weber</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Department of Immunology,</institution><institution>University of Tübingen,</institution></institution-wrap>Auf der Morgenstelle 15, 72076 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Auf der Morgenstelle 15, 72076 Tübingen</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Psoriasis is an inflammatory skin disease with strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37. LL37 in complex with DNA and RNA is thought to initiate disease exacerbation via plasmacytoid dendritic cells. However, the source of nucleic acids supposed to start this initial inflammatory event remains unknown. We show here that primary murine and human PMNs mount a fulminant and self-propagating neutrophil extracellular trap (NET) and cytokine response, but independently of the canonical NET component, DNA. Unexpectedly, RNA, which is abundant in NETs and psoriatic but not healthy skin, in complex with LL37 triggered TLR8/TLR13-mediated cytokine and NET release by PMNs in vitro and in vivo. Transfer of NETs to naive human PMNs prompts additional NET release, promoting further inflammation. Our study thus uncovers a self-propagating vicious cycle contributing to chronic inflammation in psoriasis, and NET-associated RNA (naRNA) as a physiologically relevant NET component.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Griffiths, Ce" uniqKey="Griffiths C">CE Griffiths</name></author><author><name sortKey="Barker, Jn" uniqKey="Barker J">JN Barker</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Sen, Bilge Bulbul" uniqKey="Sen B">Bilge Bulbul Sen</name></author><author><name sortKey="Rifaioglu, Emine Nur" uniqKey="Rifaioglu E">Emine Nur Rifaioglu</name></author><author><name sortKey="Ekiz, Ozlem" uniqKey="Ekiz O">Ozlem Ekiz</name></author><author><name sortKey="Inan, Mehmet Ugur" uniqKey="Inan M">Mehmet Ugur Inan</name></author><author><name sortKey="Sen, Tugba" uniqKey="Sen T">Tugba Sen</name></author><author><name sortKey="Sen, Nihat" uniqKey="Sen N">Nihat 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sortKey="Kreikemeyer, B" uniqKey="Kreikemeyer B">B Kreikemeyer</name></author><author><name sortKey="Dalpke, Ah" uniqKey="Dalpke A">AH Dalpke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berger, M" uniqKey="Berger M">M Berger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lindau, D" uniqKey="Lindau D">D Lindau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Janke, M" uniqKey="Janke M">M Janke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuznik, A" uniqKey="Kuznik A">A Kuznik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schmidt, Nw" uniqKey="Schmidt N">NW Schmidt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsukura, S" uniqKey="Matsukura S">S Matsukura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alekseyenko, Av" uniqKey="Alekseyenko A">AV Alekseyenko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eigenbrod, T" uniqKey="Eigenbrod T">T Eigenbrod</name></author><author><name sortKey="Dalpke, Ah" uniqKey="Dalpke A">AH Dalpke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cruikshank, W" uniqKey="Cruikshank W">W Cruikshank</name></author><author><name sortKey="Little, F" uniqKey="Little F">F Little</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roth, S" uniqKey="Roth S">S Roth</name></author><author><name sortKey="Solbach, W" uniqKey="Solbach W">W Solbach</name></author><author><name sortKey="Laskay, T" uniqKey="Laskay T">T Laskay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menten, P" uniqKey="Menten P">P Menten</name></author><author><name sortKey="Wuyts, A" uniqKey="Wuyts A">A Wuyts</name></author><author><name sortKey="Van Damme, J" uniqKey="Van 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature Communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31913271</article-id><article-id pub-id-type="pmc">6949246</article-id><article-id pub-id-type="publisher-id">13756</article-id><article-id pub-id-type="doi">10.1038/s41467-019-13756-4</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-1512-7306</contrib-id><name><surname>Herster</surname><given-names>Franziska</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bittner</surname><given-names>Zsofia</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Archer</surname><given-names>Nathan K.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Dickhöfer</surname><given-names>Sabine</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Eisel</surname><given-names>David</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff14">14</xref></contrib><contrib contrib-type="author"><name><surname>Eigenbrod</surname><given-names>Tatjana</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Knorpp</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-6785-181X</contrib-id><name><surname>Schneiderhan-Marra</surname><given-names>Nicole</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-2513-1317</contrib-id><name><surname>Löffler</surname><given-names>Markus W.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff5">5</xref><xref ref-type="aff" rid="Aff6">6</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-7862-277X</contrib-id><name><surname>Kalbacher</surname><given-names>Hubert</given-names></name><xref ref-type="aff" rid="Aff7">7</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-3110-4155</contrib-id><name><surname>Vierbuchen</surname><given-names>Tim</given-names></name><xref ref-type="aff" rid="Aff8">8</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-8128-5068</contrib-id><name><surname>Heine</surname><given-names>Holger</given-names></name><xref ref-type="aff" rid="Aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>Miller</surname><given-names>Lloyd S.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Hartl</surname><given-names>Dominik</given-names></name><xref ref-type="aff" rid="Aff9">9</xref><xref ref-type="aff" rid="Aff10">10</xref></contrib><contrib contrib-type="author"><name><surname>Freund</surname><given-names>Lukas</given-names></name><xref ref-type="aff" rid="Aff11">11</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-6344-7799</contrib-id><name><surname>Schäkel</surname><given-names>Knut</given-names></name><xref ref-type="aff" rid="Aff11">11</xref></contrib><contrib contrib-type="author"><name><surname>Heister</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="Aff12">12</xref></contrib><contrib contrib-type="author"><name><surname>Ghoreschi</surname><given-names>Kamran</given-names></name><xref ref-type="aff" rid="Aff12">12</xref><xref ref-type="aff" rid="Aff13">13</xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-8627-7056</contrib-id><name><surname>Weber</surname><given-names>Alexander N. R.</given-names></name><address><email>alexander.weber@uni-tuebingen.de</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Department of Immunology,</institution><institution>University of Tübingen,</institution></institution-wrap>Auf der Morgenstelle 15, 72076 Tübingen, Germany</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2171 9311</institution-id><institution-id institution-id-type="GRID">grid.21107.35</institution-id><institution>Department of Dermatology,</institution><institution>Johns Hopkins University School of Medicine,</institution></institution-wrap>Baltimore, MD 21231 USA</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0328 4908</institution-id><institution-id institution-id-type="GRID">grid.5253.1</institution-id><institution>Department of Infectious Diseases, Medical Microbiology and Hygiene,</institution><institution>University Hospital Heidelberg,</institution></institution-wrap>Im Neuenheimer Feld 324, 69120 Heidelberg, Germany</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9457 1306</institution-id><institution-id institution-id-type="GRID">grid.461765.7</institution-id><institution>NMI Natural and Medical Sciences Institute at the University of Tübingen,</institution></institution-wrap>Markwiesenstr. 55, 72770 Reutlingen, Germany</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0196 8249</institution-id><institution-id institution-id-type="GRID">grid.411544.1</institution-id><institution>Department of General, Visceral and Transplant Surgery,</institution><institution>University Hospital Tübingen,</institution></institution-wrap>Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0196 8249</institution-id><institution-id institution-id-type="GRID">grid.411544.1</institution-id><institution>Department of Clinical Pharmacology,</institution><institution>University Hospital Tübingen,</institution></institution-wrap>Auf der Morgenstelle 8, 72076 Tübingen, Germany</aff><aff id="Aff7"><label>7</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Interfaculty Institute of Biochemistry, University of Tübingen,</institution></institution-wrap>Hoppe-Seyler-Str. 4, 72076 Tübingen, Germany</aff><aff id="Aff8"><label>8</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0493 9170</institution-id><institution-id institution-id-type="GRID">grid.418187.3</institution-id><institution>Research Group Innate Immunity, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Deutsches Zentrum für Lungenforschung (DZL),</institution></institution-wrap>Parkallee 22, 23845 Borstel, Germany</aff><aff id="Aff9"><label>9</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>University Children’s Hospital and Interdisciplinary Center for Infectious Diseases, University of Tübingen,</institution></institution-wrap>Hoppe-Seyler-Str. 1, 72076 Tübingen, Germany</aff><aff id="Aff10"><label>10</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 1515 9979</institution-id><institution-id institution-id-type="GRID">grid.419481.1</institution-id><institution>Novartis Institutes for BioMedical Research (NIBR),</institution></institution-wrap>Basel, Switzerland</aff><aff id="Aff11"><label>11</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0328 4908</institution-id><institution-id institution-id-type="GRID">grid.5253.1</institution-id><institution>Department of Dermatology,</institution><institution>University Hospital Heidelberg,</institution></institution-wrap>Im Neuenheimer Feld 440, 69120 Heidelberg, Germany</aff><aff id="Aff12"><label>12</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0196 8249</institution-id><institution-id institution-id-type="GRID">grid.411544.1</institution-id><institution>Department of Dermatology,</institution><institution>University Hospital Tübingen,</institution></institution-wrap>Liebermeisterstr. 25, 72076 Tübingen, Germany</aff><aff id="Aff13"><label>13</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2218 4662</institution-id><institution-id institution-id-type="GRID">grid.6363.0</institution-id><institution>Department of Dermatology, Charité – Universitätsmedizin Berlin,</institution></institution-wrap>Charitéplatz 1, 10117 Berlin, Germany</aff><aff id="Aff14"><label>14</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 4692 2203</institution-id><institution-id institution-id-type="GRID">grid.434484.b</institution-id><institution>Present Address: David Eisel, BioNTech,</institution></institution-wrap>An der Goldgrube 12, 55131 Mainz, Germany</aff></contrib-group><pub-date pub-type="epub"><day>8</day><month>1</month><year>2020</year></pub-date><pub-date pub-type="pmc-release"><day>8</day><month>1</month><year>2020</year></pub-date><pub-date pub-type="collection"><year>2020</year></pub-date><volume>11</volume><elocation-id>105</elocation-id><history><date date-type="received"><day>10</day><month>8</month><year>2018</year></date><date date-type="accepted"><day>13</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>© The Author(s) 2020</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Psoriasis is an inflammatory skin disease with strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37. LL37 in complex with DNA and RNA is thought to initiate disease exacerbation via plasmacytoid dendritic cells. However, the source of nucleic acids supposed to start this initial inflammatory event remains unknown. We show here that primary murine and human PMNs mount a fulminant and self-propagating neutrophil extracellular trap (NET) and cytokine response, but independently of the canonical NET component, DNA. Unexpectedly, RNA, which is abundant in NETs and psoriatic but not healthy skin, in complex with LL37 triggered TLR8/TLR13-mediated cytokine and NET release by PMNs in vitro and in vivo. Transfer of NETs to naive human PMNs prompts additional NET release, promoting further inflammation. Our study thus uncovers a self-propagating vicious cycle contributing to chronic inflammation in psoriasis, and NET-associated RNA (naRNA) as a physiologically relevant NET component.</p></abstract><abstract id="Abs2" abstract-type="web-summary"><p id="Par2">Antimicrobial peptide LL37 can bind nucleic acids and potentiate their sensing by endosomal TLRs. Here the authors show that LL37 binds to RNA from neutrophil extracellular traps (NETs), which amplifies inflammation and production of more LL37 and NETs via TLR8/13, suggesting that LL37 contribution to psoriasis may be fueled by NET-associated RNA.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Chronic inflammation</kwd><kwd>Neutrophils</kwd><kwd>Toll-like receptors</kwd><kwd>Skin diseases</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100001659</institution-id><institution>Deutsche Forschungsgemeinschaft (German Research Foundation)</institution></institution-wrap></funding-source><award-id>TR156 Project B05</award-id><award-id>TR156 Project B05</award-id><award-id>TR156 Project B05</award-id><principal-award-recipient><name><surname>Herster</surname><given-names>Franziska</given-names></name><name><surname>Bittner</surname><given-names>Zsofia</given-names></name><name><surname>Weber</surname><given-names>Alexander N. R.</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100002345</institution-id><institution>Eberhard Karls Universität Tübingen (University of Tübingen)</institution></institution-wrap></funding-source></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100009397</institution-id><institution>University of Tübingen | Medizinischen Fakultät, Eberhard Karls Universität Tübingen (Faculty of Medicine, University of Tübingen)</institution></institution-wrap></funding-source></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2020</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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