AP1S3 Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production
Identifieur interne : 002521 ( Main/Exploration ); précédent : 002520; suivant : 002522AP1S3 Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production
Auteurs : Satveer K. Mahil [Royaume-Uni] ; Sophie Twelves [Royaume-Uni] ; Katalin Farkas [Hongrie] ; Niovi Setta-Kaffetzi [Royaume-Uni] ; A. David Burden [Royaume-Uni] ; Joanna E. Gach [Royaume-Uni] ; Alan D. Irvine [Irlande (pays)] ; Lászl Képír [Hongrie] ; Maja Mockenhaupt [Allemagne] ; Hazel H. Oon [Singapour] ; Jason Pinner [Australie] ; Annamari Ranki [Finlande] ; Marieke M. B. Seyger [Pays-Bas] ; Pere Soler-Palacin [Espagne] ; Eoin R. Storan [Irlande (pays)] ; Eugene S. Tan [Singapour] ; Laurence Valeyrie-Allanore [France] ; Helen S. Young [Royaume-Uni] ; Richard C. Trembath [Royaume-Uni] ; Siew-Eng Choon [Malaisie] ; Marta Szell [Hongrie] ; Zsuzsanna Bata-Csorgo [Hongrie] ; Catherine H. Smith [Royaume-Uni] ; Paola Di Meglio [Royaume-Uni] ; Jonathan N. Barker [Royaume-Uni] ; Francesca Capon [Royaume-Uni]Source :
- The Journal of Investigative Dermatology [ 0022-202X ] ; 2016.
Descripteurs français
- KwdFr :
- ADN (génétique), Activation de la transcription, Adulte d'âge moyen, Analyse de mutations d'ADN, Autophagie, Femelle, Humains, Interleukine-1 (biosynthèse), Interleukine-1 (génétique), Kératinocytes (anatomopathologie), Kératinocytes (métabolisme), Lignée cellulaire, Mutation, Protéines adaptatrices de la transduction du signal (génétique), Protéines adaptatrices de la transduction du signal (métabolisme), Psoriasis (anatomopathologie), Psoriasis (génétique), Psoriasis (métabolisme), Régulation positive, Sujet âgé, Transduction du signal.
- MESH :
- anatomopathologie : Kératinocytes, Psoriasis.
- biosynthèse : Interleukine-1.
- génétique : ADN, Interleukine-1, Protéines adaptatrices de la transduction du signal, Psoriasis.
- métabolisme : Kératinocytes, Protéines adaptatrices de la transduction du signal, Psoriasis.
- Activation de la transcription, Adulte d'âge moyen, Analyse de mutations d'ADN, Autophagie, Femelle, Humains, Lignée cellulaire, Mutation, Régulation positive, Sujet âgé, Transduction du signal.
English descriptors
- KwdEn :
- Adaptor Proteins, Signal Transducing (genetics), Adaptor Proteins, Signal Transducing (metabolism), Aged, Autophagy, Cell Line, DNA (genetics), DNA Mutational Analysis, Female, Humans, Interleukin-1 (biosynthesis), Interleukin-1 (genetics), Keratinocytes (metabolism), Keratinocytes (pathology), Middle Aged, Mutation, Psoriasis (genetics), Psoriasis (metabolism), Psoriasis (pathology), Signal Transduction, Transcriptional Activation, Up-Regulation.
- MESH :
- chemical , biosynthesis : Interleukin-1.
- chemical , genetics : Adaptor Proteins, Signal Transducing, DNA, Interleukin-1.
- chemical , metabolism : Adaptor Proteins, Signal Transducing.
- genetics : Psoriasis.
- metabolism : Keratinocytes, Psoriasis.
- pathology : Keratinocytes, Psoriasis.
- Aged, Autophagy, Cell Line, DNA Mutational Analysis, Female, Humans, Middle Aged, Mutation, Signal Transduction, Transcriptional Activation, Up-Regulation.
Abstract
Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting
Url:
DOI: 10.1016/j.jid.2016.06.618
PubMed: 27388993
PubMed Central: 5070969
Affiliations:
- Allemagne, Australie, Espagne, Finlande, France, Hongrie, Irlande (pays), Malaisie, Pays-Bas, Royaume-Uni, Singapour
- Angleterre, Bade-Wurtemberg, Catalogne, District de Fribourg-en-Brisgau, Grand Londres, Grand Manchester, Gueldre, Midlands de l'Ouest, Écosse, Île-de-France
- Barcelone, Birmingham, Fribourg-en-Brisgau, Glasgow, Londres, Manchester, Nimègue, Paris
- Université de Glasgow, Université de Manchester
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Le document en format XML
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Irvine</name><affiliation wicri:level="1"><nlm:aff id="aff5">Paediatric Dermatology, Our Lady’s Children’s Hospital, Dublin, Ireland</nlm:aff><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Paediatric Dermatology, Our Lady’s Children’s Hospital, Dublin</wicri:regionArea><wicri:noRegion>Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Kepir, Laszl" sort="Kepir, Laszl" uniqKey="Kepir L" first="Lászl" last="Képír">Lászl Képír</name><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Dermatology and Allergology, University of Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>Department of Dermatology and Allergology, University of Szeged</wicri:regionArea><wicri:noRegion>University of Szeged</wicri:noRegion></affiliation></author><author><name sortKey="Mockenhaupt, Maja" sort="Mockenhaupt, Maja" uniqKey="Mockenhaupt M" first="Maja" last="Mockenhaupt">Maja Mockenhaupt</name><affiliation wicri:level="3"><nlm:aff id="aff7">Dokumentationszentrum schwerer Hautreaktionen (dZh) and RegiSCAR-study, Department of Dermatology, Medical Center–University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Dokumentationszentrum schwerer Hautreaktionen (dZh) and RegiSCAR-study, Department of Dermatology, Medical Center–University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Oon, Hazel H" sort="Oon, Hazel H" uniqKey="Oon H" first="Hazel H." last="Oon">Hazel H. Oon</name><affiliation wicri:level="1"><nlm:aff id="aff8">National Skin Centre, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>National Skin Centre</wicri:regionArea></affiliation></author><author><name sortKey="Pinner, Jason" sort="Pinner, Jason" uniqKey="Pinner J" first="Jason" last="Pinner">Jason Pinner</name><affiliation wicri:level="1"><nlm:aff id="aff9">Department of Medical Genomics, Royal Prince Alfred Hospital, Camperdown, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Genomics, Royal Prince Alfred Hospital, Camperdown</wicri:regionArea><wicri:noRegion>Camperdown</wicri:noRegion></affiliation></author><author><name sortKey="Ranki, Annamari" sort="Ranki, Annamari" uniqKey="Ranki A" first="Annamari" last="Ranki">Annamari Ranki</name><affiliation wicri:level="1"><nlm:aff id="aff10">Department of Skin and Allergic Diseases, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Skin and Allergic Diseases, Helsinki University Central Hospital, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Seyger, Marieke M B" sort="Seyger, Marieke M B" uniqKey="Seyger M" first="Marieke M. B." last="Seyger">Marieke M. B. Seyger</name><affiliation wicri:level="3"><nlm:aff id="aff11">Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Soler Palacin, Pere" sort="Soler Palacin, Pere" uniqKey="Soler Palacin P" first="Pere" last="Soler-Palacin">Pere Soler-Palacin</name><affiliation wicri:level="3"><nlm:aff id="aff12">Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Storan, Eoin R" sort="Storan, Eoin R" uniqKey="Storan E" first="Eoin R." last="Storan">Eoin R. Storan</name><affiliation wicri:level="1"><nlm:aff id="aff13">Department of Dermatology, University Hospital, Galway, Ireland</nlm:aff><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Department of Dermatology, University Hospital, Galway</wicri:regionArea><wicri:noRegion>Galway</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Eugene S" sort="Tan, Eugene S" uniqKey="Tan E" first="Eugene S." last="Tan">Eugene S. Tan</name><affiliation wicri:level="1"><nlm:aff id="aff8">National Skin Centre, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>National Skin Centre</wicri:regionArea></affiliation></author><author><name sortKey="Valeyrie Allanore, Laurence" sort="Valeyrie Allanore, Laurence" uniqKey="Valeyrie Allanore L" first="Laurence" last="Valeyrie-Allanore">Laurence Valeyrie-Allanore</name><affiliation wicri:level="3"><nlm:aff id="aff14">Department of Dermatology, Henri Mondor Hospital, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Dermatology, Henri Mondor Hospital, 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="Young, Helen S" sort="Young, Helen S" uniqKey="Young H" first="Helen S." last="Young">Helen S. Young</name><affiliation wicri:level="4"><nlm:aff id="aff15">Department of Dermatology, University of Manchester</nlm:aff><country>Royaume-Uni</country><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName><orgName type="university">Université de Manchester</orgName></affiliation></author><author><name sortKey="Trembath, Richard C" sort="Trembath, Richard C" uniqKey="Trembath R" first="Richard C." last="Trembath">Richard C. Trembath</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Choon, Siew Eng" sort="Choon, Siew Eng" uniqKey="Choon S" first="Siew-Eng" last="Choon">Siew-Eng Choon</name><affiliation wicri:level="1"><nlm:aff id="aff16">Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Malaysia</nlm:aff><country xml:lang="fr">Malaisie</country><wicri:regionArea>Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru</wicri:regionArea><wicri:noRegion>Johor Bahru</wicri:noRegion></affiliation></author><author><name sortKey="Szell, Marta" sort="Szell, Marta" uniqKey="Szell M" first="Marta" last="Szell">Marta Szell</name><affiliation wicri:level="1"><nlm:aff id="aff2">MTA-SZTE Dermatological Research Group, Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>MTA-SZTE Dermatological Research Group, Szeged</wicri:regionArea><wicri:noRegion>Szeged</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff17">Institute of Medical Genetics, University of Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>Institute of Medical Genetics, University of Szeged</wicri:regionArea><wicri:noRegion>University of Szeged</wicri:noRegion></affiliation></author><author><name sortKey="Bata Csorgo, Zsuzsanna" sort="Bata Csorgo, Zsuzsanna" uniqKey="Bata Csorgo Z" first="Zsuzsanna" last="Bata-Csorgo">Zsuzsanna Bata-Csorgo</name><affiliation wicri:level="1"><nlm:aff id="aff2">MTA-SZTE Dermatological Research Group, Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>MTA-SZTE Dermatological Research Group, Szeged</wicri:regionArea><wicri:noRegion>Szeged</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Dermatology and Allergology, University of Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>Department of Dermatology and Allergology, University of Szeged</wicri:regionArea><wicri:noRegion>University of Szeged</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Catherine H" sort="Smith, Catherine H" uniqKey="Smith C" first="Catherine H." last="Smith">Catherine H. Smith</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Di Meglio, Paola" sort="Di Meglio, Paola" uniqKey="Di Meglio P" first="Paola" last="Di Meglio">Paola Di Meglio</name><affiliation wicri:level="3"><nlm:aff id="aff18">Mill Hill Laboratory, The Francis Crick Institute, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Mill Hill Laboratory, The Francis Crick Institute, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Barker, Jonathan N" sort="Barker, Jonathan N" uniqKey="Barker J" first="Jonathan N." last="Barker">Jonathan N. Barker</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Capon, Francesca" sort="Capon, Francesca" uniqKey="Capon F" first="Francesca" last="Capon">Francesca Capon</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27388993</idno><idno type="pmc">5070969</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070969</idno><idno type="RBID">PMC:5070969</idno><idno type="doi">10.1016/j.jid.2016.06.618</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">002688</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002688</idno><idno type="wicri:Area/Pmc/Curation">002538</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002538</idno><idno type="wicri:Area/Pmc/Checkpoint">000C03</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000C03</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">001673</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001673</idno><idno type="wicri:Area/PubMed/Curation">001651</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001651</idno><idno type="wicri:Area/PubMed/Checkpoint">001651</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001651</idno><idno type="wicri:Area/Ncbi/Merge">003813</idno><idno type="wicri:Area/Ncbi/Curation">003813</idno><idno type="wicri:Area/Ncbi/Checkpoint">003813</idno><idno type="wicri:Area/Main/Merge">002520</idno><idno type="wicri:Area/Main/Curation">002521</idno><idno type="wicri:Area/Main/Exploration">002521</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>AP1S3</italic> Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production</title><author><name sortKey="Mahil, Satveer K" sort="Mahil, Satveer K" uniqKey="Mahil S" first="Satveer K." last="Mahil">Satveer K. Mahil</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Twelves, Sophie" sort="Twelves, Sophie" uniqKey="Twelves S" first="Sophie" last="Twelves">Sophie Twelves</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Farkas, Katalin" sort="Farkas, Katalin" uniqKey="Farkas K" first="Katalin" last="Farkas">Katalin Farkas</name><affiliation wicri:level="1"><nlm:aff id="aff2">MTA-SZTE Dermatological Research Group, Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>MTA-SZTE Dermatological Research Group, Szeged</wicri:regionArea><wicri:noRegion>Szeged</wicri:noRegion></affiliation></author><author><name sortKey="Setta Kaffetzi, Niovi" sort="Setta Kaffetzi, Niovi" uniqKey="Setta Kaffetzi N" first="Niovi" last="Setta-Kaffetzi">Niovi Setta-Kaffetzi</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Burden, A David" sort="Burden, A David" uniqKey="Burden A" first="A. David" last="Burden">A. David Burden</name><affiliation wicri:level="4"><nlm:aff id="aff3">Department of Dermatology, University of Glasgow, Glasgow, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Dermatology, University of Glasgow, Glasgow</wicri:regionArea><orgName type="university">Université de Glasgow</orgName><placeName><settlement type="city">Glasgow</settlement><region type="country">Écosse</region></placeName></affiliation></author><author><name sortKey="Gach, Joanna E" sort="Gach, Joanna E" uniqKey="Gach J" first="Joanna E." last="Gach">Joanna E. Gach</name><affiliation wicri:level="3"><nlm:aff id="aff4">Department of Dermatology, Birmingham Children’s Hospital, Birmingham, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Dermatology, Birmingham Children’s Hospital, Birmingham</wicri:regionArea><placeName><settlement type="city">Birmingham</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Midlands de l'Ouest</region></placeName></affiliation></author><author><name sortKey="Irvine, Alan D" sort="Irvine, Alan D" uniqKey="Irvine A" first="Alan D." last="Irvine">Alan D. Irvine</name><affiliation wicri:level="1"><nlm:aff id="aff5">Paediatric Dermatology, Our Lady’s Children’s Hospital, Dublin, Ireland</nlm:aff><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Paediatric Dermatology, Our Lady’s Children’s Hospital, Dublin</wicri:regionArea><wicri:noRegion>Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Kepir, Laszl" sort="Kepir, Laszl" uniqKey="Kepir L" first="Lászl" last="Képír">Lászl Képír</name><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Dermatology and Allergology, University of Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>Department of Dermatology and Allergology, University of Szeged</wicri:regionArea><wicri:noRegion>University of Szeged</wicri:noRegion></affiliation></author><author><name sortKey="Mockenhaupt, Maja" sort="Mockenhaupt, Maja" uniqKey="Mockenhaupt M" first="Maja" last="Mockenhaupt">Maja Mockenhaupt</name><affiliation wicri:level="3"><nlm:aff id="aff7">Dokumentationszentrum schwerer Hautreaktionen (dZh) and RegiSCAR-study, Department of Dermatology, Medical Center–University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Dokumentationszentrum schwerer Hautreaktionen (dZh) and RegiSCAR-study, Department of Dermatology, Medical Center–University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Oon, Hazel H" sort="Oon, Hazel H" uniqKey="Oon H" first="Hazel H." last="Oon">Hazel H. Oon</name><affiliation wicri:level="1"><nlm:aff id="aff8">National Skin Centre, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>National Skin Centre</wicri:regionArea></affiliation></author><author><name sortKey="Pinner, Jason" sort="Pinner, Jason" uniqKey="Pinner J" first="Jason" last="Pinner">Jason Pinner</name><affiliation wicri:level="1"><nlm:aff id="aff9">Department of Medical Genomics, Royal Prince Alfred Hospital, Camperdown, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Genomics, Royal Prince Alfred Hospital, Camperdown</wicri:regionArea><wicri:noRegion>Camperdown</wicri:noRegion></affiliation></author><author><name sortKey="Ranki, Annamari" sort="Ranki, Annamari" uniqKey="Ranki A" first="Annamari" last="Ranki">Annamari Ranki</name><affiliation wicri:level="1"><nlm:aff id="aff10">Department of Skin and Allergic Diseases, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Skin and Allergic Diseases, Helsinki University Central Hospital, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Seyger, Marieke M B" sort="Seyger, Marieke M B" uniqKey="Seyger M" first="Marieke M. B." last="Seyger">Marieke M. B. Seyger</name><affiliation wicri:level="3"><nlm:aff id="aff11">Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Soler Palacin, Pere" sort="Soler Palacin, Pere" uniqKey="Soler Palacin P" first="Pere" last="Soler-Palacin">Pere Soler-Palacin</name><affiliation wicri:level="3"><nlm:aff id="aff12">Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Storan, Eoin R" sort="Storan, Eoin R" uniqKey="Storan E" first="Eoin R." last="Storan">Eoin R. Storan</name><affiliation wicri:level="1"><nlm:aff id="aff13">Department of Dermatology, University Hospital, Galway, Ireland</nlm:aff><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Department of Dermatology, University Hospital, Galway</wicri:regionArea><wicri:noRegion>Galway</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Eugene S" sort="Tan, Eugene S" uniqKey="Tan E" first="Eugene S." last="Tan">Eugene S. Tan</name><affiliation wicri:level="1"><nlm:aff id="aff8">National Skin Centre, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>National Skin Centre</wicri:regionArea></affiliation></author><author><name sortKey="Valeyrie Allanore, Laurence" sort="Valeyrie Allanore, Laurence" uniqKey="Valeyrie Allanore L" first="Laurence" last="Valeyrie-Allanore">Laurence Valeyrie-Allanore</name><affiliation wicri:level="3"><nlm:aff id="aff14">Department of Dermatology, Henri Mondor Hospital, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Dermatology, Henri Mondor Hospital, 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="Young, Helen S" sort="Young, Helen S" uniqKey="Young H" first="Helen S." last="Young">Helen S. Young</name><affiliation wicri:level="4"><nlm:aff id="aff15">Department of Dermatology, University of Manchester</nlm:aff><country>Royaume-Uni</country><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName><orgName type="university">Université de Manchester</orgName></affiliation></author><author><name sortKey="Trembath, Richard C" sort="Trembath, Richard C" uniqKey="Trembath R" first="Richard C." last="Trembath">Richard C. Trembath</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Choon, Siew Eng" sort="Choon, Siew Eng" uniqKey="Choon S" first="Siew-Eng" last="Choon">Siew-Eng Choon</name><affiliation wicri:level="1"><nlm:aff id="aff16">Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Malaysia</nlm:aff><country xml:lang="fr">Malaisie</country><wicri:regionArea>Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru</wicri:regionArea><wicri:noRegion>Johor Bahru</wicri:noRegion></affiliation></author><author><name sortKey="Szell, Marta" sort="Szell, Marta" uniqKey="Szell M" first="Marta" last="Szell">Marta Szell</name><affiliation wicri:level="1"><nlm:aff id="aff2">MTA-SZTE Dermatological Research Group, Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>MTA-SZTE Dermatological Research Group, Szeged</wicri:regionArea><wicri:noRegion>Szeged</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff17">Institute of Medical Genetics, University of Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>Institute of Medical Genetics, University of Szeged</wicri:regionArea><wicri:noRegion>University of Szeged</wicri:noRegion></affiliation></author><author><name sortKey="Bata Csorgo, Zsuzsanna" sort="Bata Csorgo, Zsuzsanna" uniqKey="Bata Csorgo Z" first="Zsuzsanna" last="Bata-Csorgo">Zsuzsanna Bata-Csorgo</name><affiliation wicri:level="1"><nlm:aff id="aff2">MTA-SZTE Dermatological Research Group, Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>MTA-SZTE Dermatological Research Group, Szeged</wicri:regionArea><wicri:noRegion>Szeged</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Dermatology and Allergology, University of Szeged, Hungary</nlm:aff><country xml:lang="fr">Hongrie</country><wicri:regionArea>Department of Dermatology and Allergology, University of Szeged</wicri:regionArea><wicri:noRegion>University of Szeged</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Catherine H" sort="Smith, Catherine H" uniqKey="Smith C" first="Catherine H." last="Smith">Catherine H. Smith</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Di Meglio, Paola" sort="Di Meglio, Paola" uniqKey="Di Meglio P" first="Paola" last="Di Meglio">Paola Di Meglio</name><affiliation wicri:level="3"><nlm:aff id="aff18">Mill Hill Laboratory, The Francis Crick Institute, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Mill Hill Laboratory, The Francis Crick Institute, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Barker, Jonathan N" sort="Barker, Jonathan N" uniqKey="Barker J" first="Jonathan N." last="Barker">Jonathan N. Barker</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Capon, Francesca" sort="Capon, Francesca" uniqKey="Capon F" first="Francesca" last="Capon">Francesca Capon</name><affiliation wicri:level="3"><nlm:aff id="aff1">Division of Genetics and Molecular Medicine, King’s College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Molecular Medicine, King’s College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of Investigative Dermatology</title><idno type="ISSN">0022-202X</idno><idno type="eISSN">1523-1747</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptor Proteins, Signal Transducing (genetics)</term><term>Adaptor Proteins, Signal Transducing (metabolism)</term><term>Aged</term><term>Autophagy</term><term>Cell Line</term><term>DNA (genetics)</term><term>DNA Mutational Analysis</term><term>Female</term><term>Humans</term><term>Interleukin-1 (biosynthesis)</term><term>Interleukin-1 (genetics)</term><term>Keratinocytes (metabolism)</term><term>Keratinocytes (pathology)</term><term>Middle Aged</term><term>Mutation</term><term>Psoriasis (genetics)</term><term>Psoriasis (metabolism)</term><term>Psoriasis (pathology)</term><term>Signal Transduction</term><term>Transcriptional Activation</term><term>Up-Regulation</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN (génétique)</term><term>Activation de la transcription</term><term>Adulte d'âge moyen</term><term>Analyse de mutations d'ADN</term><term>Autophagie</term><term>Femelle</term><term>Humains</term><term>Interleukine-1 (biosynthèse)</term><term>Interleukine-1 (génétique)</term><term>Kératinocytes (anatomopathologie)</term><term>Kératinocytes (métabolisme)</term><term>Lignée cellulaire</term><term>Mutation</term><term>Protéines adaptatrices de la transduction du signal (génétique)</term><term>Protéines adaptatrices de la transduction du signal (métabolisme)</term><term>Psoriasis (anatomopathologie)</term><term>Psoriasis (génétique)</term><term>Psoriasis (métabolisme)</term><term>Régulation positive</term><term>Sujet âgé</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Interleukin-1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term><term>DNA</term><term>Interleukin-1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Kératinocytes</term><term>Psoriasis</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Interleukine-1</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Psoriasis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN</term><term>Interleukine-1</term><term>Protéines adaptatrices de la transduction du signal</term><term>Psoriasis</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Keratinocytes</term><term>Psoriasis</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Kératinocytes</term><term>Protéines adaptatrices de la transduction du signal</term><term>Psoriasis</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Keratinocytes</term><term>Psoriasis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Autophagy</term><term>Cell Line</term><term>DNA Mutational Analysis</term><term>Female</term><term>Humans</term><term>Middle Aged</term><term>Mutation</term><term>Signal Transduction</term><term>Transcriptional Activation</term><term>Up-Regulation</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation de la transcription</term><term>Adulte d'âge moyen</term><term>Analyse de mutations d'ADN</term><term>Autophagie</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire</term><term>Mutation</term><term>Régulation positive</term><term>Sujet âgé</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting <italic>AP1S3</italic>, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that <italic>AP1S3</italic> expression is distinctively elevated in keratinocytes. Because <italic>AP1S3</italic> encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that <italic>AP1S3</italic> knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-κB activation. We showed that as a consequence, <italic>AP1S3</italic>-deficient cells up-regulate IL-1 signaling and overexpress IL-36α, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Aasen, T" uniqKey="Aasen T">T. Aasen</name></author><author><name sortKey="Izpisua Belmonte, J C" uniqKey="Izpisua Belmonte J">J.C. Izpisua Belmonte</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aksentijevich, I" uniqKey="Aksentijevich I">I. 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Gudjonsson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wolf, J" uniqKey="Wolf J">J. Wolf</name></author><author><name sortKey="Ferris, L K" uniqKey="Ferris L">L.K. Ferris</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Espagne</li><li>Finlande</li><li>France</li><li>Hongrie</li><li>Irlande (pays)</li><li>Malaisie</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>Singapour</li></country><region><li>Angleterre</li><li>Bade-Wurtemberg</li><li>Catalogne</li><li>District de Fribourg-en-Brisgau</li><li>Grand Londres</li><li>Grand Manchester</li><li>Gueldre</li><li>Midlands de l'Ouest</li><li>Écosse</li><li>Île-de-France</li></region><settlement><li>Barcelone</li><li>Birmingham</li><li>Fribourg-en-Brisgau</li><li>Glasgow</li><li>Londres</li><li>Manchester</li><li>Nimègue</li><li>Paris</li></settlement><orgName><li>Université de Glasgow</li><li>Université de Manchester</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Mahil, Satveer K" sort="Mahil, Satveer K" uniqKey="Mahil S" first="Satveer K." last="Mahil">Satveer K. Mahil</name></region><name sortKey="Barker, Jonathan N" sort="Barker, Jonathan N" uniqKey="Barker J" first="Jonathan N." last="Barker">Jonathan N. Barker</name><name sortKey="Burden, A David" sort="Burden, A David" uniqKey="Burden A" first="A. David" last="Burden">A. David Burden</name><name sortKey="Capon, Francesca" sort="Capon, Francesca" uniqKey="Capon F" first="Francesca" last="Capon">Francesca Capon</name><name sortKey="Di Meglio, Paola" sort="Di Meglio, Paola" uniqKey="Di Meglio P" first="Paola" last="Di Meglio">Paola Di Meglio</name><name sortKey="Gach, Joanna E" sort="Gach, Joanna E" uniqKey="Gach J" first="Joanna E." last="Gach">Joanna E. Gach</name><name sortKey="Setta Kaffetzi, Niovi" sort="Setta Kaffetzi, Niovi" uniqKey="Setta Kaffetzi N" first="Niovi" last="Setta-Kaffetzi">Niovi Setta-Kaffetzi</name><name sortKey="Smith, Catherine H" sort="Smith, Catherine H" uniqKey="Smith C" first="Catherine H." last="Smith">Catherine H. Smith</name><name sortKey="Trembath, Richard C" sort="Trembath, Richard C" uniqKey="Trembath R" first="Richard C." last="Trembath">Richard C. Trembath</name><name sortKey="Twelves, Sophie" sort="Twelves, Sophie" uniqKey="Twelves S" first="Sophie" last="Twelves">Sophie Twelves</name><name sortKey="Young, Helen S" sort="Young, Helen S" uniqKey="Young H" first="Helen S." last="Young">Helen S. Young</name></country><country name="Hongrie"><noRegion><name sortKey="Farkas, Katalin" sort="Farkas, Katalin" uniqKey="Farkas K" first="Katalin" last="Farkas">Katalin Farkas</name></noRegion><name sortKey="Bata Csorgo, Zsuzsanna" sort="Bata Csorgo, Zsuzsanna" uniqKey="Bata Csorgo Z" first="Zsuzsanna" last="Bata-Csorgo">Zsuzsanna Bata-Csorgo</name><name sortKey="Bata Csorgo, Zsuzsanna" sort="Bata Csorgo, Zsuzsanna" uniqKey="Bata Csorgo Z" first="Zsuzsanna" last="Bata-Csorgo">Zsuzsanna Bata-Csorgo</name><name sortKey="Kepir, Laszl" sort="Kepir, Laszl" uniqKey="Kepir L" first="Lászl" last="Képír">Lászl Képír</name><name sortKey="Szell, Marta" sort="Szell, Marta" uniqKey="Szell M" first="Marta" last="Szell">Marta Szell</name><name sortKey="Szell, Marta" sort="Szell, Marta" uniqKey="Szell M" first="Marta" last="Szell">Marta Szell</name></country><country name="Irlande (pays)"><noRegion><name sortKey="Irvine, Alan D" sort="Irvine, Alan D" uniqKey="Irvine A" first="Alan D." last="Irvine">Alan D. Irvine</name></noRegion><name sortKey="Storan, Eoin R" sort="Storan, Eoin R" uniqKey="Storan E" first="Eoin R." last="Storan">Eoin R. Storan</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Mockenhaupt, Maja" sort="Mockenhaupt, Maja" uniqKey="Mockenhaupt M" first="Maja" last="Mockenhaupt">Maja Mockenhaupt</name></region></country><country name="Singapour"><noRegion><name sortKey="Oon, Hazel H" sort="Oon, Hazel H" uniqKey="Oon H" first="Hazel H." last="Oon">Hazel H. Oon</name></noRegion><name sortKey="Tan, Eugene S" sort="Tan, Eugene S" uniqKey="Tan E" first="Eugene S." last="Tan">Eugene S. Tan</name></country><country name="Australie"><noRegion><name sortKey="Pinner, Jason" sort="Pinner, Jason" uniqKey="Pinner J" first="Jason" last="Pinner">Jason Pinner</name></noRegion></country><country name="Finlande"><noRegion><name sortKey="Ranki, Annamari" sort="Ranki, Annamari" uniqKey="Ranki A" first="Annamari" last="Ranki">Annamari Ranki</name></noRegion></country><country name="Pays-Bas"><region name="Gueldre"><name sortKey="Seyger, Marieke M B" sort="Seyger, Marieke M B" uniqKey="Seyger M" first="Marieke M. B." last="Seyger">Marieke M. B. Seyger</name></region></country><country name="Espagne"><region name="Catalogne"><name sortKey="Soler Palacin, Pere" sort="Soler Palacin, Pere" uniqKey="Soler Palacin P" first="Pere" last="Soler-Palacin">Pere Soler-Palacin</name></region></country><country name="France"><region name="Île-de-France"><name sortKey="Valeyrie Allanore, Laurence" sort="Valeyrie Allanore, Laurence" uniqKey="Valeyrie Allanore L" first="Laurence" last="Valeyrie-Allanore">Laurence Valeyrie-Allanore</name></region></country><country name="Malaisie"><noRegion><name sortKey="Choon, Siew Eng" sort="Choon, Siew Eng" uniqKey="Choon S" first="Siew-Eng" last="Choon">Siew-Eng Choon</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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