Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema
Identifieur interne : 003101 ( Main/Exploration ); précédent : 003100; suivant : 003102Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema
Auteurs : Tomer Avraham ; Jamie C. Zampell ; Alan Yan ; Sonia Elhadad ; Evan S. Weitman ; Stanley G. Rockson [États-Unis] ; Jacqueline Bromberg [États-Unis] ; Babak J. MehraraSource :
- The FASEB Journal [ 0892-6638 ] ; 2013.
Descripteurs français
- KwdFr :
- Animaux, Différenciation cellulaire (immunologie), Fibrose (anatomopathologie), Fibrose (génétique), Fibrose (immunologie), Inflammation (anatomopathologie), Inflammation (génétique), Inflammation (immunologie), Interleukine-13 (génétique), Interleukine-13 (immunologie), Interleukine-4 (génétique), Interleukine-4 (immunologie), Lymphocytes auxiliaires Th2 (anatomopathologie), Lymphocytes auxiliaires Th2 (immunologie), Lymphoedème (anatomopathologie), Lymphoedème (génétique), Lymphoedème (immunologie), Lymphoedème (étiologie), Modèles animaux de maladie humaine, Souris, Souris knockout, Souris nude.
- MESH :
- anatomopathologie : Fibrose, Inflammation, Lymphocytes auxiliaires Th2, Lymphoedème.
- génétique : Fibrose, Inflammation, Interleukine-13, Interleukine-4, Lymphoedème.
- immunologie : Différenciation cellulaire, Fibrose, Inflammation, Interleukine-13, Interleukine-4, Lymphocytes auxiliaires Th2, Lymphoedème.
- étiologie : Lymphoedème.
- Animaux, Modèles animaux de maladie humaine, Souris, Souris knockout, Souris nude.
English descriptors
- KwdEn :
- Animals, Cell Differentiation (immunology), Disease Models, Animal, Fibrosis (genetics), Fibrosis (immunology), Fibrosis (pathology), Inflammation (genetics), Inflammation (immunology), Inflammation (pathology), Interleukin-13 (genetics), Interleukin-13 (immunology), Interleukin-4 (genetics), Interleukin-4 (immunology), Lymphedema (etiology), Lymphedema (genetics), Lymphedema (immunology), Lymphedema (pathology), Mice, Mice, Knockout, Mice, Nude, Th2 Cells (immunology), Th2 Cells (pathology).
- MESH :
- chemical , genetics : Interleukin-13, Interleukin-4.
- etiology : Lymphedema.
- genetics : Fibrosis, Inflammation, Lymphedema.
- immunology : Cell Differentiation, Fibrosis, Inflammation, Interleukin-13, Interleukin-4, Lymphedema, Th2 Cells.
- pathology : Fibrosis, Inflammation, Lymphedema, Th2 Cells.
- Animals, Disease Models, Animal, Mice, Mice, Knockout, Mice, Nude.
Abstract
Lymphedema is a dreaded complication of cancer treatment. However, despite the fact that >5 million Americans are affected by this disorder, the development of effective treatments is limited by the fact that the pathology of lymphedema remains unknown. The purpose of these studies was to determine the role of inflammatory responses in lymphedema pathology. Using mouse models of lymphedema, as well as clinical lymphedema specimens, we show that lymphatic stasis results in a CD4+ T-cell inflammation and T-helper 2 (Th2) differentiation. Using mice deficient in T cells or CD4+ cells, we show that this inflammatory response is necessary for the pathological changes of lymphedema, including fibrosis, adipose deposition, and lymphatic dysfunction. Further, we show that inhibition of Th2 differentiation using interleukin-4 (IL-4) or IL-13 blockade prevents initiation and progression of lymphedema by decreasing tissue fibrosis and significantly improving lymphatic function, independent of lymphangiogenic growth factors. We show that CD4+ inflammation is a critical regulator of tissue fibrosis and lymphatic dysfunction in lymphedema and that inhibition of Th2 differentiation markedly improves lymphatic function independent of lymphangiogenic cytokine expression. Notably, preventing and/or reversing the development of pathological tissue changes that occur in lymphedema may be a viable treatment strategy for this disorder.—Avraham, T., Zampell, J. C., Yan, A., Elhadad, S., Weitman, E. S., Rockson, S. G., Bromberg, J., Mehrara, B. J. Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema.
Url:
DOI: 10.1096/fj.12-222695
PubMed: 23193171
PubMed Central: 3574290
Affiliations:
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Zampell</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff><wicri:noCountry code="subfield">Department of Surgery</wicri:noCountry></affiliation></author><author><name sortKey="Yan, Alan" sort="Yan, Alan" uniqKey="Yan A" first="Alan" last="Yan">Alan Yan</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff><wicri:noCountry code="subfield">Department of Surgery</wicri:noCountry></affiliation></author><author><name sortKey="Elhadad, Sonia" sort="Elhadad, Sonia" uniqKey="Elhadad S" first="Sonia" last="Elhadad">Sonia Elhadad</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff><wicri:noCountry code="subfield">Department of Surgery</wicri:noCountry></affiliation></author><author><name sortKey="Weitman, Evan S" sort="Weitman, Evan S" uniqKey="Weitman E" first="Evan S." last="Weitman">Evan S. 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Mehrara</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff><wicri:noCountry code="subfield">Department of Surgery</wicri:noCountry></affiliation></author></analytic><series><title level="j">The FASEB Journal</title><idno type="ISSN">0892-6638</idno><idno type="eISSN">1530-6860</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Differentiation (immunology)</term><term>Disease Models, Animal</term><term>Fibrosis (genetics)</term><term>Fibrosis (immunology)</term><term>Fibrosis (pathology)</term><term>Inflammation (genetics)</term><term>Inflammation (immunology)</term><term>Inflammation (pathology)</term><term>Interleukin-13 (genetics)</term><term>Interleukin-13 (immunology)</term><term>Interleukin-4 (genetics)</term><term>Interleukin-4 (immunology)</term><term>Lymphedema (etiology)</term><term>Lymphedema (genetics)</term><term>Lymphedema (immunology)</term><term>Lymphedema (pathology)</term><term>Mice</term><term>Mice, Knockout</term><term>Mice, Nude</term><term>Th2 Cells (immunology)</term><term>Th2 Cells (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Différenciation cellulaire (immunologie)</term><term>Fibrose (anatomopathologie)</term><term>Fibrose (génétique)</term><term>Fibrose (immunologie)</term><term>Inflammation (anatomopathologie)</term><term>Inflammation (génétique)</term><term>Inflammation (immunologie)</term><term>Interleukine-13 (génétique)</term><term>Interleukine-13 (immunologie)</term><term>Interleukine-4 (génétique)</term><term>Interleukine-4 (immunologie)</term><term>Lymphocytes auxiliaires Th2 (anatomopathologie)</term><term>Lymphocytes auxiliaires Th2 (immunologie)</term><term>Lymphoedème (anatomopathologie)</term><term>Lymphoedème (génétique)</term><term>Lymphoedème (immunologie)</term><term>Lymphoedème (étiologie)</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris knockout</term><term>Souris nude</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Interleukin-13</term><term>Interleukin-4</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Fibrose</term><term>Inflammation</term><term>Lymphocytes auxiliaires Th2</term><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Fibrosis</term><term>Inflammation</term><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Fibrose</term><term>Inflammation</term><term>Interleukine-13</term><term>Interleukine-4</term><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Différenciation cellulaire</term><term>Fibrose</term><term>Inflammation</term><term>Interleukine-13</term><term>Interleukine-4</term><term>Lymphocytes auxiliaires Th2</term><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cell Differentiation</term><term>Fibrosis</term><term>Inflammation</term><term>Interleukin-13</term><term>Interleukin-4</term><term>Lymphedema</term><term>Th2 Cells</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Fibrosis</term><term>Inflammation</term><term>Lymphedema</term><term>Th2 Cells</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Lymphoedème</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Mice</term><term>Mice, Knockout</term><term>Mice, Nude</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris knockout</term><term>Souris nude</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Lymphedema is a dreaded complication of cancer treatment. However, despite the fact that >5 million Americans are affected by this disorder, the development of effective treatments is limited by the fact that the pathology of lymphedema remains unknown. The purpose of these studies was to determine the role of inflammatory responses in lymphedema pathology. Using mouse models of lymphedema, as well as clinical lymphedema specimens, we show that lymphatic stasis results in a CD4<sup>+</sup> T-cell inflammation and T-helper 2 (Th2) differentiation. Using mice deficient in T cells or CD4<sup>+</sup> cells, we show that this inflammatory response is necessary for the pathological changes of lymphedema, including fibrosis, adipose deposition, and lymphatic dysfunction. Further, we show that inhibition of Th2 differentiation using interleukin-4 (IL-4) or IL-13 blockade prevents initiation and progression of lymphedema by decreasing tissue fibrosis and significantly improving lymphatic function, independent of lymphangiogenic growth factors. We show that CD4<sup>+</sup> inflammation is a critical regulator of tissue fibrosis and lymphatic dysfunction in lymphedema and that inhibition of Th2 differentiation markedly improves lymphatic function independent of lymphangiogenic cytokine expression. Notably, preventing and/or reversing the development of pathological tissue changes that occur in lymphedema may be a viable treatment strategy for this disorder.—Avraham, T., Zampell, J. C., Yan, A., Elhadad, S., Weitman, E. S., Rockson, S. G., Bromberg, J., Mehrara, B. J. Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li><li>État de New York</li></region></list><tree><noCountry><name sortKey="Avraham, Tomer" sort="Avraham, Tomer" uniqKey="Avraham T" first="Tomer" last="Avraham">Tomer Avraham</name><name sortKey="Elhadad, Sonia" sort="Elhadad, Sonia" uniqKey="Elhadad S" first="Sonia" last="Elhadad">Sonia Elhadad</name><name sortKey="Mehrara, Babak J" sort="Mehrara, Babak J" uniqKey="Mehrara B" first="Babak J." last="Mehrara">Babak J. Mehrara</name><name sortKey="Weitman, Evan S" sort="Weitman, Evan S" uniqKey="Weitman E" first="Evan S." last="Weitman">Evan S. Weitman</name><name sortKey="Yan, Alan" sort="Yan, Alan" uniqKey="Yan A" first="Alan" last="Yan">Alan Yan</name><name sortKey="Zampell, Jamie C" sort="Zampell, Jamie C" uniqKey="Zampell J" first="Jamie C." last="Zampell">Jamie C. Zampell</name></noCountry><country name="États-Unis"><region name="Californie"><name sortKey="Rockson, Stanley G" sort="Rockson, Stanley G" uniqKey="Rockson S" first="Stanley G." last="Rockson">Stanley G. Rockson</name></region><name sortKey="Bromberg, Jacqueline" sort="Bromberg, Jacqueline" uniqKey="Bromberg J" first="Jacqueline" last="Bromberg">Jacqueline Bromberg</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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