Neutralisation of the interleukin-33/ST2 pathway ameliorates experimental colitis through enhancement of mucosal healing in mice
Identifieur interne : 004896 ( Main/Exploration ); précédent : 004895; suivant : 004897Neutralisation of the interleukin-33/ST2 pathway ameliorates experimental colitis through enhancement of mucosal healing in mice
Auteurs : Mamdouh A K. Sedhom [Australie] ; Mélanie Pichery [France] ; Jenna R. Murdoch [Suisse] ; Benoit Foligné [France] ; Nathalie Ortega [France] ; Sylvain Normand [France] ; Kirsten Mertz [Suisse] ; Devika Sanmugalingam [Suisse] ; Lea Brault ; Teddy Grandjean [France] ; Emma Lefrancais [France] ; Padraic G. Fallon [Irlande (pays)] ; Valérie Quesniaux ; Laurent Peyrin-Biroulet [France] ; Gieri Cathomas [Suisse] ; Tobias Junt [Suisse] ; Mathias Chamaillard [France] ; Jean-Philippe Girard [France] ; Bernhard Ryffel [France]Source :
- Gut [ 0017-5749 ] ; 2013-12.
Descripteurs français
- Wicri :
- topic : Eau potable.
English descriptors
- KwdEn :
- Active disease, Adaptive immunity, Apoptotic caspases, Biopsy, Biopsy forceps, Bone marrow cells, Bone marrow transplantation, Bowel, Bowel disease, Bowel diseases, Chimaeric animals, Colitis, Colon, Colon homogenates, Colon length, Colonic, Colonic epithelia, Colonic epithelium, Colonic mucosa, Colonic sections, Control animals, Cytokine, Cytokine network, Dextran, Dextran sodium mice, Dextran sodium sulphate, Dextran sodium sulphate colitis, Disease activity index, Disease severity, Double staining, Drinking water, Endothelial cells, Epithelial, Epithelial barrier function, Epithelial cells, Epithelium, Experimental colitis, Experimental colitis figure, Experimental models, Genetic ablation, Gure, Histological, Histological score, Human bowel diseases, Immunohistochemical analysis, Immunol, Independent experiments, Innate lymphoid cells, Intestinal, Intestinal barrier function, Intestinal epithelium, Intestinal homeostasis, Intestinal permeability, Isotype control, Junction intercellular communication, Lamina propria, Mouse, Mucosal, Mucosal regeneration, Multiple comparison test, Ndings, Neutralisation, Neutralising antibody, Nuclear factor, Online, Pathway, Permeability, Polyclonal, Proc natl acad, Relative mrna expression, Remission, Room temperature, Sedhom, Size bars, Smooth muscle actin, Ulcerative colitis, Wound healing.
- Teeft :
- Active disease, Adaptive immunity, Apoptotic caspases, Biopsy, Biopsy forceps, Bone marrow cells, Bone marrow transplantation, Bowel, Bowel disease, Bowel diseases, Chimaeric animals, Colitis, Colon, Colon homogenates, Colon length, Colonic, Colonic epithelia, Colonic epithelium, Colonic mucosa, Colonic sections, Control animals, Cytokine, Cytokine network, Dextran, Dextran sodium mice, Dextran sodium sulphate, Dextran sodium sulphate colitis, Disease activity index, Disease severity, Double staining, Drinking water, Endothelial cells, Epithelial, Epithelial barrier function, Epithelial cells, Epithelium, Experimental colitis, Experimental colitis figure, Experimental models, Genetic ablation, Gure, Histological, Histological score, Human bowel diseases, Immunohistochemical analysis, Immunol, Independent experiments, Innate lymphoid cells, Intestinal, Intestinal barrier function, Intestinal epithelium, Intestinal homeostasis, Intestinal permeability, Isotype control, Junction intercellular communication, Lamina propria, Mouse, Mucosal, Mucosal regeneration, Multiple comparison test, Ndings, Neutralisation, Neutralising antibody, Nuclear factor, Online, Pathway, Permeability, Polyclonal, Proc natl acad, Relative mrna expression, Remission, Room temperature, Sedhom, Size bars, Smooth muscle actin, Ulcerative colitis, Wound healing.
Abstract
Objective Inflammatory bowel diseases (IBD) have been intrinsically linked to a deregulated cytokine network, but novel therapeutic principles are urgently needed. Here we identify the interleukin (IL)-33 and its receptor ST2 as key negative regulators of wound healing and permeability in the colon of mice. Design Expression of IL-33 and ST2 was determined by qRT-PCR, ELISA, immunohistochemistry and western-blot analysis. Wild-type and St2−/− mice were used in wound healing experiments and in two experimental models of IBD triggered by 2,4,6-trinitrobenzene sulphonic acid or dextran sodium sulphate (DSS). Neutralisation of ST2 was performed by using a specific blocking antibody. Results Nuclear localisation and enhanced expression of IL-33 in myofibroblasts and enterocytes was linked to disease involvement independently of inflammation, while the expression of ST2 was primarily restricted to the colonic epithelia. In two experimental models of IBD, genetic ablation of ST2 significantly improved signs of colitis, while a sustained epithelial expression of the cyto-protective factor connexin-43 was observed in DSS-treated St2-deficient mice. Unexpectedly, absence of ST2 in non-hematopoietic cells was sufficient to protect against colitis. Consistently, specific inhibition of endogenous ST2-mediated signalling by treatment with neutralising antibody improved DSS-induced colitis. In addition, IL-33 treatment impaired epithelial barrier permeability in vitro and in vivo, whereas absence of ST2 enhanced wound healing response upon acute mechanical injury in the colon. Conclusions Our study unveiled a novel non-hematopoietic function of IL-33 in epithelial barrier function and wound healing. Therefore, blocking the IL-33/ST2 axis may represent an efficient therapy in IBD.
Url:
- https://api.istex.fr/document/24397C364AA5D797E8DC279ECBAAD52CDEC11091/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841767
DOI: 10.1136/gutjnl-2011-301785
Affiliations:
- Australie, France, Irlande (pays), Suisse
- Centre-Val de Loire, Grand Est, Hauts-de-France, Lorraine (région), Midi-Pyrénées, Nord-Pas-de-Calais, Occitanie (région administrative), Région Centre
- Lille, Nancy, Orléans, Toulouse, Vandœuvre-lès-Nancy
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Le document en format XML
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wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur de Lille, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>University Lille Nord de France, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>CNRS, UMR 8204, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U1019, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Lefrancais, Emma" sort="Lefrancais, Emma" uniqKey="Lefrancais E" first="Emma" last="Lefrancais">Emma Lefrancais</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>CNRS, IPBS, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Toulouse University, UPS, F-31077 Toulouse</wicri:regionArea><wicri:noRegion>31077 Toulouse</wicri:noRegion><wicri:noRegion>F-31077 Toulouse</wicri:noRegion></affiliation></author><author><name sortKey="Fallon, Padraic G" sort="Fallon, Padraic G" uniqKey="Fallon P" first="Padraic G" last="Fallon">Padraic G. Fallon</name><affiliation wicri:level="1"><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>School of Medicine, Trinity College, Dublin</wicri:regionArea><wicri:noRegion>Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Quesniaux, Valerie" sort="Quesniaux, Valerie" uniqKey="Quesniaux V" first="Valérie" last="Quesniaux">Valérie Quesniaux</name><affiliation><wicri:noCountry code="subField">RSA</wicri:noCountry></affiliation></author><author><name sortKey="Peyrin Biroulet, Laurent" sort="Peyrin Biroulet, Laurent" uniqKey="Peyrin Biroulet L" first="Laurent" last="Peyrin-Biroulet">Laurent Peyrin-Biroulet</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Inserm U954, University Hospital of Nancy, Vandoeuvre-lès-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Cathomas, Gieri" sort="Cathomas, Gieri" uniqKey="Cathomas G" first="Gieri" last="Cathomas">Gieri Cathomas</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pathology, Kantonsspital Baselland, Liestal</wicri:regionArea><wicri:noRegion>Liestal</wicri:noRegion></affiliation></author><author><name sortKey="Junt, Tobias" sort="Junt, Tobias" uniqKey="Junt T" first="Tobias" last="Junt">Tobias Junt</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Autoimmunity, Transplantation and Inflammation, Novartis Institute for Biomedical Research, Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></affiliation></author><author><name sortKey="Chamaillard, Mathias" sort="Chamaillard, Mathias" uniqKey="Chamaillard M" 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type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U1019, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Girard, Jean Philippe" sort="Girard, Jean Philippe" uniqKey="Girard J" first="Jean-Philippe" last="Girard">Jean-Philippe Girard</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>CNRS, IPBS, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Toulouse University, UPS, F-31077 Toulouse</wicri:regionArea><wicri:noRegion>31077 Toulouse</wicri:noRegion><wicri:noRegion>F-31077 Toulouse</wicri:noRegion></affiliation></author><author><name sortKey="Ryffel, Bernhard" sort="Ryffel, Bernhard" uniqKey="Ryffel B" first="Bernhard" last="Ryffel">Bernhard Ryffel</name><affiliation></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Artimmune SAS, Orléans</wicri:regionArea><placeName><region type="region">Centre-Val de Loire</region><region type="old region">Région Centre</region><settlement type="city">Orléans</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Gut</title><title level="j" type="abbrev">Gut</title><idno type="ISSN">0017-5749</idno><idno type="eISSN">1468-3288</idno><imprint><publisher>BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><date type="published" when="2013-12">2013-12</date><biblScope unit="volume">62</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1714">1714</biblScope></imprint><idno type="ISSN">0017-5749</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0017-5749</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Active disease</term><term>Adaptive immunity</term><term>Apoptotic caspases</term><term>Biopsy</term><term>Biopsy forceps</term><term>Bone marrow cells</term><term>Bone marrow transplantation</term><term>Bowel</term><term>Bowel disease</term><term>Bowel diseases</term><term>Chimaeric animals</term><term>Colitis</term><term>Colon</term><term>Colon homogenates</term><term>Colon length</term><term>Colonic</term><term>Colonic epithelia</term><term>Colonic epithelium</term><term>Colonic mucosa</term><term>Colonic sections</term><term>Control animals</term><term>Cytokine</term><term>Cytokine network</term><term>Dextran</term><term>Dextran sodium mice</term><term>Dextran sodium sulphate</term><term>Dextran sodium sulphate colitis</term><term>Disease activity index</term><term>Disease severity</term><term>Double staining</term><term>Drinking water</term><term>Endothelial cells</term><term>Epithelial</term><term>Epithelial barrier function</term><term>Epithelial cells</term><term>Epithelium</term><term>Experimental colitis</term><term>Experimental colitis figure</term><term>Experimental models</term><term>Genetic ablation</term><term>Gure</term><term>Histological</term><term>Histological score</term><term>Human bowel diseases</term><term>Immunohistochemical analysis</term><term>Immunol</term><term>Independent experiments</term><term>Innate lymphoid cells</term><term>Intestinal</term><term>Intestinal barrier function</term><term>Intestinal epithelium</term><term>Intestinal homeostasis</term><term>Intestinal permeability</term><term>Isotype control</term><term>Junction intercellular communication</term><term>Lamina propria</term><term>Mouse</term><term>Mucosal</term><term>Mucosal regeneration</term><term>Multiple comparison test</term><term>Ndings</term><term>Neutralisation</term><term>Neutralising antibody</term><term>Nuclear factor</term><term>Online</term><term>Pathway</term><term>Permeability</term><term>Polyclonal</term><term>Proc natl acad</term><term>Relative mrna expression</term><term>Remission</term><term>Room temperature</term><term>Sedhom</term><term>Size bars</term><term>Smooth muscle actin</term><term>Ulcerative colitis</term><term>Wound healing</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Active disease</term><term>Adaptive immunity</term><term>Apoptotic caspases</term><term>Biopsy</term><term>Biopsy forceps</term><term>Bone marrow cells</term><term>Bone marrow transplantation</term><term>Bowel</term><term>Bowel disease</term><term>Bowel diseases</term><term>Chimaeric animals</term><term>Colitis</term><term>Colon</term><term>Colon homogenates</term><term>Colon length</term><term>Colonic</term><term>Colonic epithelia</term><term>Colonic epithelium</term><term>Colonic mucosa</term><term>Colonic sections</term><term>Control animals</term><term>Cytokine</term><term>Cytokine network</term><term>Dextran</term><term>Dextran sodium mice</term><term>Dextran sodium sulphate</term><term>Dextran sodium sulphate colitis</term><term>Disease activity index</term><term>Disease severity</term><term>Double staining</term><term>Drinking water</term><term>Endothelial cells</term><term>Epithelial</term><term>Epithelial barrier function</term><term>Epithelial cells</term><term>Epithelium</term><term>Experimental colitis</term><term>Experimental colitis figure</term><term>Experimental models</term><term>Genetic ablation</term><term>Gure</term><term>Histological</term><term>Histological score</term><term>Human bowel diseases</term><term>Immunohistochemical analysis</term><term>Immunol</term><term>Independent experiments</term><term>Innate lymphoid cells</term><term>Intestinal</term><term>Intestinal barrier function</term><term>Intestinal epithelium</term><term>Intestinal homeostasis</term><term>Intestinal permeability</term><term>Isotype control</term><term>Junction intercellular communication</term><term>Lamina propria</term><term>Mouse</term><term>Mucosal</term><term>Mucosal regeneration</term><term>Multiple comparison test</term><term>Ndings</term><term>Neutralisation</term><term>Neutralising antibody</term><term>Nuclear factor</term><term>Online</term><term>Pathway</term><term>Permeability</term><term>Polyclonal</term><term>Proc natl acad</term><term>Relative mrna expression</term><term>Remission</term><term>Room temperature</term><term>Sedhom</term><term>Size bars</term><term>Smooth muscle actin</term><term>Ulcerative colitis</term><term>Wound healing</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Eau potable</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Objective Inflammatory bowel diseases (IBD) have been intrinsically linked to a deregulated cytokine network, but novel therapeutic principles are urgently needed. Here we identify the interleukin (IL)-33 and its receptor ST2 as key negative regulators of wound healing and permeability in the colon of mice. Design Expression of IL-33 and ST2 was determined by qRT-PCR, ELISA, immunohistochemistry and western-blot analysis. Wild-type and St2−/− mice were used in wound healing experiments and in two experimental models of IBD triggered by 2,4,6-trinitrobenzene sulphonic acid or dextran sodium sulphate (DSS). Neutralisation of ST2 was performed by using a specific blocking antibody. Results Nuclear localisation and enhanced expression of IL-33 in myofibroblasts and enterocytes was linked to disease involvement independently of inflammation, while the expression of ST2 was primarily restricted to the colonic epithelia. In two experimental models of IBD, genetic ablation of ST2 significantly improved signs of colitis, while a sustained epithelial expression of the cyto-protective factor connexin-43 was observed in DSS-treated St2-deficient mice. Unexpectedly, absence of ST2 in non-hematopoietic cells was sufficient to protect against colitis. Consistently, specific inhibition of endogenous ST2-mediated signalling by treatment with neutralising antibody improved DSS-induced colitis. In addition, IL-33 treatment impaired epithelial barrier permeability in vitro and in vivo, whereas absence of ST2 enhanced wound healing response upon acute mechanical injury in the colon. Conclusions Our study unveiled a novel non-hematopoietic function of IL-33 in epithelial barrier function and wound healing. Therefore, blocking the IL-33/ST2 axis may represent an efficient therapy in IBD.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Irlande (pays)</li><li>Suisse</li></country><region><li>Centre-Val de Loire</li><li>Grand Est</li><li>Hauts-de-France</li><li>Lorraine (région)</li><li>Midi-Pyrénées</li><li>Nord-Pas-de-Calais</li><li>Occitanie (région administrative)</li><li>Région Centre</li></region><settlement><li>Lille</li><li>Nancy</li><li>Orléans</li><li>Toulouse</li><li>Vandœuvre-lès-Nancy</li></settlement></list><tree><noCountry><name sortKey="Brault, Lea" sort="Brault, Lea" uniqKey="Brault L" first="Lea" last="Brault">Lea Brault</name><name sortKey="Quesniaux, Valerie" sort="Quesniaux, Valerie" uniqKey="Quesniaux V" first="Valérie" last="Quesniaux">Valérie Quesniaux</name></noCountry><country name="Australie"><noRegion><name sortKey="Sedhom, Mamdouh A K" sort="Sedhom, Mamdouh A K" uniqKey="Sedhom M" first="Mamdouh A K" last="Sedhom">Mamdouh A K. Sedhom</name></noRegion></country><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Pichery, Melanie" sort="Pichery, Melanie" uniqKey="Pichery M" first="Mélanie" last="Pichery">Mélanie Pichery</name></region><name sortKey="Chamaillard, Mathias" sort="Chamaillard, Mathias" uniqKey="Chamaillard M" first="Mathias" last="Chamaillard">Mathias Chamaillard</name><name sortKey="Chamaillard, Mathias" sort="Chamaillard, Mathias" uniqKey="Chamaillard M" first="Mathias" last="Chamaillard">Mathias Chamaillard</name><name sortKey="Chamaillard, Mathias" sort="Chamaillard, Mathias" uniqKey="Chamaillard M" first="Mathias" last="Chamaillard">Mathias Chamaillard</name><name sortKey="Chamaillard, Mathias" sort="Chamaillard, Mathias" uniqKey="Chamaillard M" first="Mathias" last="Chamaillard">Mathias Chamaillard</name><name sortKey="Foligne, Benoit" sort="Foligne, Benoit" uniqKey="Foligne B" first="Benoit" last="Foligné">Benoit Foligné</name><name sortKey="Foligne, Benoit" sort="Foligne, Benoit" uniqKey="Foligne B" first="Benoit" last="Foligné">Benoit Foligné</name><name sortKey="Foligne, Benoit" sort="Foligne, Benoit" uniqKey="Foligne B" first="Benoit" last="Foligné">Benoit Foligné</name><name sortKey="Foligne, Benoit" sort="Foligne, Benoit" uniqKey="Foligne B" first="Benoit" last="Foligné">Benoit Foligné</name><name sortKey="Girard, Jean Philippe" sort="Girard, Jean Philippe" uniqKey="Girard J" first="Jean-Philippe" last="Girard">Jean-Philippe Girard</name><name sortKey="Girard, Jean Philippe" sort="Girard, Jean Philippe" uniqKey="Girard J" first="Jean-Philippe" last="Girard">Jean-Philippe Girard</name><name sortKey="Grandjean, Teddy" sort="Grandjean, Teddy" uniqKey="Grandjean T" first="Teddy" last="Grandjean">Teddy Grandjean</name><name sortKey="Grandjean, Teddy" sort="Grandjean, Teddy" uniqKey="Grandjean T" first="Teddy" last="Grandjean">Teddy Grandjean</name><name sortKey="Grandjean, Teddy" sort="Grandjean, Teddy" uniqKey="Grandjean T" first="Teddy" last="Grandjean">Teddy Grandjean</name><name sortKey="Grandjean, Teddy" sort="Grandjean, Teddy" uniqKey="Grandjean T" first="Teddy" last="Grandjean">Teddy Grandjean</name><name sortKey="Lefrancais, Emma" sort="Lefrancais, Emma" uniqKey="Lefrancais E" first="Emma" last="Lefrancais">Emma Lefrancais</name><name sortKey="Lefrancais, Emma" sort="Lefrancais, Emma" uniqKey="Lefrancais E" first="Emma" last="Lefrancais">Emma Lefrancais</name><name sortKey="Normand, Sylvain" sort="Normand, Sylvain" uniqKey="Normand S" first="Sylvain" last="Normand">Sylvain Normand</name><name sortKey="Normand, Sylvain" sort="Normand, Sylvain" uniqKey="Normand S" first="Sylvain" last="Normand">Sylvain Normand</name><name sortKey="Normand, Sylvain" sort="Normand, Sylvain" uniqKey="Normand S" first="Sylvain" last="Normand">Sylvain Normand</name><name sortKey="Normand, Sylvain" sort="Normand, Sylvain" uniqKey="Normand S" first="Sylvain" last="Normand">Sylvain Normand</name><name sortKey="Ortega, Nathalie" sort="Ortega, Nathalie" uniqKey="Ortega N" first="Nathalie" last="Ortega">Nathalie Ortega</name><name sortKey="Ortega, Nathalie" sort="Ortega, Nathalie" uniqKey="Ortega N" first="Nathalie" last="Ortega">Nathalie Ortega</name><name sortKey="Peyrin Biroulet, Laurent" sort="Peyrin Biroulet, Laurent" uniqKey="Peyrin Biroulet L" first="Laurent" last="Peyrin-Biroulet">Laurent Peyrin-Biroulet</name><name sortKey="Pichery, Melanie" sort="Pichery, Melanie" uniqKey="Pichery M" first="Mélanie" last="Pichery">Mélanie Pichery</name><name sortKey="Ryffel, Bernhard" sort="Ryffel, Bernhard" uniqKey="Ryffel B" first="Bernhard" last="Ryffel">Bernhard Ryffel</name></country><country name="Suisse"><noRegion><name sortKey="Murdoch, Jenna R" sort="Murdoch, Jenna R" uniqKey="Murdoch J" first="Jenna R" last="Murdoch">Jenna R. Murdoch</name></noRegion><name sortKey="Cathomas, Gieri" sort="Cathomas, Gieri" uniqKey="Cathomas G" first="Gieri" last="Cathomas">Gieri Cathomas</name><name sortKey="Junt, Tobias" sort="Junt, Tobias" uniqKey="Junt T" first="Tobias" last="Junt">Tobias Junt</name><name sortKey="Mertz, Kirsten" sort="Mertz, Kirsten" uniqKey="Mertz K" first="Kirsten" last="Mertz">Kirsten Mertz</name><name sortKey="Sanmugalingam, Devika" sort="Sanmugalingam, Devika" uniqKey="Sanmugalingam D" first="Devika" last="Sanmugalingam">Devika Sanmugalingam</name></country><country name="Irlande (pays)"><noRegion><name sortKey="Fallon, Padraic G" sort="Fallon, Padraic G" uniqKey="Fallon P" first="Padraic G" last="Fallon">Padraic G. Fallon</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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