Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4(+) T Cells Drives the Pathogenesis of Lymphedema.
Identifieur interne : 000912 ( PubMed/Curation ); précédent : 000911; suivant : 000913Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4(+) T Cells Drives the Pathogenesis of Lymphedema.
Auteurs : Fusa Ogata [Japon] ; Katsuhito Fujiu [Japon] ; Sahohime Matsumoto [Japon] ; Yukiteru Nakayama [Japon] ; Munehiko Shibata [Japon] ; Yuichi Oike [Japon] ; Isao Koshima [Japon] ; Tetsuro Watabe [Japon] ; Ryozo Nagai [Japon] ; Ichiro Manabe [Japon]Source :
- The Journal of investigative dermatology [ 1523-1747 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Cellules cultivées, Facteur de croissance endothéliale vasculaire de type A (métabolisme), Immunohistochimie, Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase (pharmacologie), Lymphangiogenèse (physiologie), Lymphocytes T CD4+ (), Lymphocytes T CD4+ (métabolisme), Lymphoedème (anatomopathologie), Lymphoedème (immunologie), Macrophages (cytologie), Macrophages (immunologie), Modèles animaux de maladie humaine, Ponction-biopsie à l'aiguille, Sensibilité et spécificité, Souris.
- MESH :
- anatomopathologie : Lymphoedème.
- cytologie : Macrophages.
- immunologie : Lymphoedème, Macrophages.
- métabolisme : Facteur de croissance endothéliale vasculaire de type A, Lymphocytes T CD4+.
- pharmacologie : Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase.
- physiologie : Lymphangiogenèse.
- Animaux, Cellules cultivées, Immunohistochimie, Lymphocytes T CD4+, Modèles animaux de maladie humaine, Ponction-biopsie à l'aiguille, Sensibilité et spécificité, Souris.
English descriptors
- KwdEn :
- Animals, Biopsy, Needle, CD4-Positive T-Lymphocytes (drug effects), CD4-Positive T-Lymphocytes (metabolism), Cells, Cultured, Disease Models, Animal, Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology), Immunohistochemistry, Lymphangiogenesis (physiology), Lymphedema (immunology), Lymphedema (pathology), Macrophages (cytology), Macrophages (immunology), Mice, Sensitivity and Specificity, Vascular Endothelial Growth Factor A (metabolism).
- MESH :
- chemical , metabolism : Vascular Endothelial Growth Factor A.
- chemical , pharmacology : Hydroxymethylglutaryl-CoA Reductase Inhibitors.
- cytology : Macrophages.
- drug effects : CD4-Positive T-Lymphocytes.
- immunology : Lymphedema, Macrophages.
- metabolism : CD4-Positive T-Lymphocytes.
- pathology : Lymphedema.
- physiology : Lymphangiogenesis.
- Animals, Biopsy, Needle, Cells, Cultured, Disease Models, Animal, Immunohistochemistry, Mice, Sensitivity and Specificity.
Abstract
Lymphedema is a debilitating progressive condition that severely restricts quality of life and is frequently observed after cancer surgery. The mechanism underlying lymphedema development remains poorly understood, and no effective pharmacological means to prevent or alleviate the ailment is currently available. Using a mouse model of lymphedema, we show here that excessive generation of immature lymphatic vessels is essential for initial edema development and that this early process is also important for later development of lymphedema pathology. We found that CD4(+) T cells interact with macrophages to promote lymphangiogenesis, and that both lymphangiogenesis and edema were greatly reduced in macrophage-depleted mice, lymphocyte-deficient Rag2(?/?) mice or CD4(+) T-cell-deficient mice. Mechanistically, T helper type 1 and T helper type 17 cells activate lesional macrophages to produce vascular endothelial growth factor-C, which promotes lymphangiogenesis, and inhibition of this mechanism suppressed not only early lymphangiogenesis, but also later development of lymphedema. Finally, we show that atorvastatin suppresses excessive lymphangiogenesis and lymphedema by inhibiting T helper type 1 and T helper type 17 cell activation. These results demonstrate that the interaction between CD4(+) T cells and macrophages is a potential therapeutic target for prevention of lymphedema after surgery.
DOI: 10.1016/j.jid.2015.12.001
PubMed: 27015456
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000912
Links to Exploration step
pubmed:27015456Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4(+) T Cells Drives the Pathogenesis of Lymphedema.</title><author><name sortKey="Ogata, Fusa" sort="Ogata, Fusa" uniqKey="Ogata F" first="Fusa" last="Ogata">Fusa Ogata</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Fujiu, Katsuhito" sort="Fujiu, Katsuhito" uniqKey="Fujiu K" first="Katsuhito" last="Fujiu">Katsuhito Fujiu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Matsumoto, Sahohime" sort="Matsumoto, Sahohime" uniqKey="Matsumoto S" first="Sahohime" last="Matsumoto">Sahohime Matsumoto</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Nakayama, Yukiteru" sort="Nakayama, Yukiteru" uniqKey="Nakayama Y" first="Yukiteru" last="Nakayama">Yukiteru Nakayama</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Shibata, Munehiko" sort="Shibata, Munehiko" uniqKey="Shibata M" first="Munehiko" last="Shibata">Munehiko Shibata</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Oike, Yuichi" sort="Oike, Yuichi" uniqKey="Oike Y" first="Yuichi" last="Oike">Yuichi Oike</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto</wicri:regionArea></affiliation></author><author><name sortKey="Koshima, Isao" sort="Koshima, Isao" uniqKey="Koshima I" first="Isao" last="Koshima">Isao Koshima</name><affiliation wicri:level="1"><nlm:affiliation>Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Watabe, Tetsuro" sort="Watabe, Tetsuro" uniqKey="Watabe T" first="Tetsuro" last="Watabe">Tetsuro Watabe</name><affiliation wicri:level="1"><nlm:affiliation>Section of Cellular Biochemistry, Department of Bio-matrix, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Section of Cellular Biochemistry, Department of Bio-matrix, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Nagai, Ryozo" sort="Nagai, Ryozo" uniqKey="Nagai R" first="Ryozo" last="Nagai">Ryozo Nagai</name><affiliation wicri:level="1"><nlm:affiliation>Jichi Medical University, Yakushiji, Shimotsuke-shi, Tochigi, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Jichi Medical University, Yakushiji, Shimotsuke-shi, Tochigi</wicri:regionArea></affiliation></author><author><name sortKey="Manabe, Ichiro" sort="Manabe, Ichiro" uniqKey="Manabe I" first="Ichiro" last="Manabe">Ichiro Manabe</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Aging Research, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan. Electronic address: manabe-tky@umin.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Aging Research, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27015456</idno><idno type="pmid">27015456</idno><idno type="doi">10.1016/j.jid.2015.12.001</idno><idno type="wicri:Area/PubMed/Corpus">000912</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000912</idno><idno type="wicri:Area/PubMed/Curation">000912</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000912</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4(+) T Cells Drives the Pathogenesis of Lymphedema.</title><author><name sortKey="Ogata, Fusa" sort="Ogata, Fusa" uniqKey="Ogata F" first="Fusa" last="Ogata">Fusa Ogata</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Fujiu, Katsuhito" sort="Fujiu, Katsuhito" uniqKey="Fujiu K" first="Katsuhito" last="Fujiu">Katsuhito Fujiu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Matsumoto, Sahohime" sort="Matsumoto, Sahohime" uniqKey="Matsumoto S" first="Sahohime" last="Matsumoto">Sahohime Matsumoto</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Nakayama, Yukiteru" sort="Nakayama, Yukiteru" uniqKey="Nakayama Y" first="Yukiteru" last="Nakayama">Yukiteru Nakayama</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Shibata, Munehiko" sort="Shibata, Munehiko" uniqKey="Shibata M" first="Munehiko" last="Shibata">Munehiko Shibata</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Oike, Yuichi" sort="Oike, Yuichi" uniqKey="Oike Y" first="Yuichi" last="Oike">Yuichi Oike</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto</wicri:regionArea></affiliation></author><author><name sortKey="Koshima, Isao" sort="Koshima, Isao" uniqKey="Koshima I" first="Isao" last="Koshima">Isao Koshima</name><affiliation wicri:level="1"><nlm:affiliation>Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Watabe, Tetsuro" sort="Watabe, Tetsuro" uniqKey="Watabe T" first="Tetsuro" last="Watabe">Tetsuro Watabe</name><affiliation wicri:level="1"><nlm:affiliation>Section of Cellular Biochemistry, Department of Bio-matrix, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Section of Cellular Biochemistry, Department of Bio-matrix, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Nagai, Ryozo" sort="Nagai, Ryozo" uniqKey="Nagai R" first="Ryozo" last="Nagai">Ryozo Nagai</name><affiliation wicri:level="1"><nlm:affiliation>Jichi Medical University, Yakushiji, Shimotsuke-shi, Tochigi, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Jichi Medical University, Yakushiji, Shimotsuke-shi, Tochigi</wicri:regionArea></affiliation></author><author><name sortKey="Manabe, Ichiro" sort="Manabe, Ichiro" uniqKey="Manabe I" first="Ichiro" last="Manabe">Ichiro Manabe</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Aging Research, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan. Electronic address: manabe-tky@umin.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Aging Research, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba</wicri:regionArea></affiliation></author></analytic><series><title level="j">The Journal of investigative dermatology</title><idno type="eISSN">1523-1747</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Biopsy, Needle</term><term>CD4-Positive T-Lymphocytes (drug effects)</term><term>CD4-Positive T-Lymphocytes (metabolism)</term><term>Cells, Cultured</term><term>Disease Models, Animal</term><term>Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)</term><term>Immunohistochemistry</term><term>Lymphangiogenesis (physiology)</term><term>Lymphedema (immunology)</term><term>Lymphedema (pathology)</term><term>Macrophages (cytology)</term><term>Macrophages (immunology)</term><term>Mice</term><term>Sensitivity and Specificity</term><term>Vascular Endothelial Growth Factor A (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Facteur de croissance endothéliale vasculaire de type A (métabolisme)</term><term>Immunohistochimie</term><term>Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase (pharmacologie)</term><term>Lymphangiogenèse (physiologie)</term><term>Lymphocytes T CD4+ ()</term><term>Lymphocytes T CD4+ (métabolisme)</term><term>Lymphoedème (anatomopathologie)</term><term>Lymphoedème (immunologie)</term><term>Macrophages (cytologie)</term><term>Macrophages (immunologie)</term><term>Modèles animaux de maladie humaine</term><term>Ponction-biopsie à l'aiguille</term><term>Sensibilité et spécificité</term><term>Souris</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Vascular Endothelial Growth Factor A</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Hydroxymethylglutaryl-CoA Reductase Inhibitors</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphoedème</term><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Lymphedema</term><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de croissance endothéliale vasculaire de type A</term><term>Lymphocytes T CD4+</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Lymphangiogenèse</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Lymphangiogenesis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biopsy, Needle</term><term>Cells, Cultured</term><term>Disease Models, Animal</term><term>Immunohistochemistry</term><term>Mice</term><term>Sensitivity and Specificity</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Immunohistochimie</term><term>Lymphocytes T CD4+</term><term>Modèles animaux de maladie humaine</term><term>Ponction-biopsie à l'aiguille</term><term>Sensibilité et spécificité</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lymphedema is a debilitating progressive condition that severely restricts quality of life and is frequently observed after cancer surgery. The mechanism underlying lymphedema development remains poorly understood, and no effective pharmacological means to prevent or alleviate the ailment is currently available. Using a mouse model of lymphedema, we show here that excessive generation of immature lymphatic vessels is essential for initial edema development and that this early process is also important for later development of lymphedema pathology. We found that CD4(+) T cells interact with macrophages to promote lymphangiogenesis, and that both lymphangiogenesis and edema were greatly reduced in macrophage-depleted mice, lymphocyte-deficient Rag2(?/?) mice or CD4(+) T-cell-deficient mice. Mechanistically, T helper type 1 and T helper type 17 cells activate lesional macrophages to produce vascular endothelial growth factor-C, which promotes lymphangiogenesis, and inhibition of this mechanism suppressed not only early lymphangiogenesis, but also later development of lymphedema. Finally, we show that atorvastatin suppresses excessive lymphangiogenesis and lymphedema by inhibiting T helper type 1 and T helper type 17 cell activation. These results demonstrate that the interaction between CD4(+) T cells and macrophages is a potential therapeutic target for prevention of lymphedema after surgery.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27015456</PMID><DateCreated><Year>2016</Year><Month>03</Month><Day>26</Day></DateCreated><DateCompleted><Year>2016</Year><Month>07</Month><Day>11</Day></DateCompleted><DateRevised><Year>2016</Year><Month>03</Month><Day>26</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1523-1747</ISSN><JournalIssue CitedMedium="Internet"><Volume>136</Volume><Issue>3</Issue><PubDate><Year>2016</Year><Month>Mar</Month></PubDate></JournalIssue><Title>The Journal of investigative dermatology</Title><ISOAbbreviation>J. Invest. Dermatol.</ISOAbbreviation></Journal><ArticleTitle>Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4(+) T Cells Drives the Pathogenesis of Lymphedema.</ArticleTitle><Pagination><MedlinePgn>706-14</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jid.2015.12.001</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0022-202X(15)00092-5</ELocationID><Abstract><AbstractText>Lymphedema is a debilitating progressive condition that severely restricts quality of life and is frequently observed after cancer surgery. The mechanism underlying lymphedema development remains poorly understood, and no effective pharmacological means to prevent or alleviate the ailment is currently available. Using a mouse model of lymphedema, we show here that excessive generation of immature lymphatic vessels is essential for initial edema development and that this early process is also important for later development of lymphedema pathology. We found that CD4(+) T cells interact with macrophages to promote lymphangiogenesis, and that both lymphangiogenesis and edema were greatly reduced in macrophage-depleted mice, lymphocyte-deficient Rag2(?/?) mice or CD4(+) T-cell-deficient mice. Mechanistically, T helper type 1 and T helper type 17 cells activate lesional macrophages to produce vascular endothelial growth factor-C, which promotes lymphangiogenesis, and inhibition of this mechanism suppressed not only early lymphangiogenesis, but also later development of lymphedema. Finally, we show that atorvastatin suppresses excessive lymphangiogenesis and lymphedema by inhibiting T helper type 1 and T helper type 17 cell activation. These results demonstrate that the interaction between CD4(+) T cells and macrophages is a potential therapeutic target for prevention of lymphedema after surgery.</AbstractText><CopyrightInformation>Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ogata</LastName><ForeName>Fusa</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fujiu</LastName><ForeName>Katsuhito</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Matsumoto</LastName><ForeName>Sahohime</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, Hongo, Bunkyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nakayama</LastName><ForeName>Yukiteru</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shibata</LastName><ForeName>Munehiko</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oike</LastName><ForeName>Yuichi</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koshima</LastName><ForeName>Isao</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Plastic and Reconstruction Surgery, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Watabe</LastName><ForeName>Tetsuro</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Section of Cellular Biochemistry, Department of Bio-matrix, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nagai</LastName><ForeName>Ryozo</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Jichi Medical University, Yakushiji, Shimotsuke-shi, Tochigi, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Manabe</LastName><ForeName>Ichiro</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Medicine, the University of Tokyo, Hongo, Bunkyo, Tokyo, Japan; Department of Aging Research, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan. Electronic address: manabe-tky@umin.ac.jp.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>12</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Invest Dermatol</MedlineTA><NlmUniqueID>0426720</NlmUniqueID><ISSNLinking>0022-202X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019161">Hydroxymethylglutaryl-CoA Reductase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D042461">Vascular Endothelial Growth Factor A</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001707" MajorTopicYN="N">Biopsy, Needle</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019161" MajorTopicYN="N">Hydroxymethylglutaryl-CoA Reductase Inhibitors</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D042583" MajorTopicYN="N">Lymphangiogenesis</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008209" MajorTopicYN="N">Lymphedema</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008264" MajorTopicYN="N">Macrophages</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012680" MajorTopicYN="N">Sensitivity and Specificity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D042461" MajorTopicYN="N">Vascular Endothelial Growth Factor A</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">LECs</Keyword><Keyword MajorTopicYN="N">T helper</Keyword><Keyword MajorTopicYN="N">Th</Keyword><Keyword MajorTopicYN="N">VEGF</Keyword><Keyword MajorTopicYN="N">VEGF receptor 3</Keyword><Keyword MajorTopicYN="N">VEGFR3</Keyword><Keyword MajorTopicYN="N">lymphatic endothelial cells</Keyword><Keyword MajorTopicYN="N">vascular endothelial growth factor</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>04</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>10</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>11</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>3</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>3</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>7</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27015456</ArticleId><ArticleId IdType="pii">S0022-202X(15)00092-5</ArticleId><ArticleId IdType="doi">10.1016/j.jid.2015.12.001</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/PubMed/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000912 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd -nk 000912 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= LymphedemaV1
|flux= PubMed
|étape= Curation
|type= RBID
|clé= pubmed:27015456
|texte= Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4(+) T Cells Drives the Pathogenesis of Lymphedema.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Curation/RBID.i -Sk "pubmed:27015456" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |