Lymph Node Transplantation Decreases Swelling and Restores Immune Responses in a Transgenic Model of Lymphedema
Identifieur interne : 000E80 ( Main/Exploration ); précédent : 000E79; suivant : 000E81Lymph Node Transplantation Decreases Swelling and Restores Immune Responses in a Transgenic Model of Lymphedema
Auteurs : Jung-Ju Huang [États-Unis, Taïwan] ; Jason C. Gardenier [États-Unis] ; Geoffrey E. Hespe [États-Unis] ; Gabriela D. García Nores [États-Unis] ; Raghu P. Kataru [États-Unis] ; Catherine L. Ly [États-Unis] ; Inés Martínez-Corral [Suède] ; Sagrario Ortega [Espagne] ; Babak J. Mehrara [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2016.
Descripteurs français
- KwdFr :
- MESH :
- anatomopathologie : Lymphoedème.
- immunologie : Lymphocytes T, Lymphoedème.
- Animaux, Humains, Lymphangiogenèse, Lymphoedème, Noeuds lymphatiques, Souris, Souris de lignée C57BL, Souris transgéniques, Vaisseaux lymphatiques.
English descriptors
- KwdEn :
- MESH :
- immunology : Lymphedema, T-Lymphocytes.
- pathology : Lymphedema.
- surgery : Lymphedema.
- transplantation : Lymph Nodes.
- Animals, Humans, Lymphangiogenesis, Lymphatic Vessels, Mice, Mice, Inbred C57BL, Mice, Transgenic.
Abstract
Secondary lymphedema is a common complication of cancer treatment and recent studies have demonstrated that lymph node transplantation (LNT) can decrease swelling, as well as the incidence of infections. However, although these results are exciting, the mechanisms by which LNT improves these pathologic findings of lymphedema remain unknown. Using a transgenic mouse model of lymphedema, this study sought to analyze the effect of LNT on lymphatic regeneration and T cell-mediated immune responses.
We used a mouse model in which the expression of the human diphtheria toxin receptor is driven by the FLT4 promoter to enable the local ablation of the lymphatic system through subdermal hindlimb diphtheria toxin injections. Popliteal lymph node dissection was subsequently performed after a two-week recovery period, followed by either orthotopic LNT or sham surgery after an additional two weeks. Hindlimb swelling, lymphatic vessel regeneration, immune cell trafficking, and T cell-mediated immune responses were analyzed 10 weeks later.
LNT resulted in a marked decrease in hindlimb swelling, fibroadipose tissue deposition, and decreased accumulation of perilymphatic inflammatory cells, as compared to controls. In addition, LNT induced a marked lymphangiogenic response in both capillary and collecting lymphatic vessels. Interestingly, the resultant regenerated lymphatics were abnormal in appearance on lymphangiography, but LNT also led to a notable increase in dendritic cell trafficking from the periphery to the inguinal lymph nodes and improved adaptive immune responses.
LNT decreases pathological changes of lymphedema and was shown to potently induce lymphangiogenesis. Lymphatic vessels induced by LNT were abnormal in appearance, but were functional and able to transport antigen-presenting cells. Animals treated with LNT have an increased ability to mount T cell-mediated immune responses when sensitized to antigens in the affected hindlimb.
Url:
DOI: 10.1371/journal.pone.0168259
PubMed: 27942023
PubMed Central: 5152898
Affiliations:
- Espagne, Suède, Taïwan, États-Unis
- Communauté de Madrid, East Middle Sweden, Svealand, État de New York
- Madrid, Uppsala
- Université d'Uppsala
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Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Humans</term>
<term>Lymph Nodes (transplantation)</term>
<term>Lymphangiogenesis</term>
<term>Lymphatic Vessels</term>
<term>Lymphedema (immunology)</term>
<term>Lymphedema (pathology)</term>
<term>Lymphedema (surgery)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>T-Lymphocytes (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Humains</term>
<term>Lymphangiogenèse</term>
<term>Lymphocytes T (immunologie)</term>
<term>Lymphoedème ()</term>
<term>Lymphoedème (anatomopathologie)</term>
<term>Lymphoedème (immunologie)</term>
<term>Noeuds lymphatiques (transplantation)</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris transgéniques</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lymphoedème</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphocytes T</term>
<term>Lymphoedème</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Lymphedema</term>
<term>T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lymphedema</term>
</keywords>
<keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Lymphedema</term>
</keywords>
<keywords scheme="MESH" qualifier="transplantation" xml:lang="en"><term>Lymph Nodes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Humans</term>
<term>Lymphangiogenesis</term>
<term>Lymphatic Vessels</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Humains</term>
<term>Lymphangiogenèse</term>
<term>Lymphoedème</term>
<term>Noeuds lymphatiques</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris transgéniques</term>
<term>Vaisseaux lymphatiques</term>
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<front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Introduction</title>
<p>Secondary lymphedema is a common complication of cancer treatment and recent studies have demonstrated that lymph node transplantation (LNT) can decrease swelling, as well as the incidence of infections. However, although these results are exciting, the mechanisms by which LNT improves these pathologic findings of lymphedema remain unknown. Using a transgenic mouse model of lymphedema, this study sought to analyze the effect of LNT on lymphatic regeneration and T cell-mediated immune responses.</p>
</sec>
<sec id="sec002"><title>Methods</title>
<p>We used a mouse model in which the expression of the human diphtheria toxin receptor is driven by the FLT4 promoter to enable the local ablation of the lymphatic system through subdermal hindlimb diphtheria toxin injections. Popliteal lymph node dissection was subsequently performed after a two-week recovery period, followed by either orthotopic LNT or sham surgery after an additional two weeks. Hindlimb swelling, lymphatic vessel regeneration, immune cell trafficking, and T cell-mediated immune responses were analyzed 10 weeks later.</p>
</sec>
<sec id="sec003"><title>Results</title>
<p>LNT resulted in a marked decrease in hindlimb swelling, fibroadipose tissue deposition, and decreased accumulation of perilymphatic inflammatory cells, as compared to controls. In addition, LNT induced a marked lymphangiogenic response in both capillary and collecting lymphatic vessels. Interestingly, the resultant regenerated lymphatics were abnormal in appearance on lymphangiography, but LNT also led to a notable increase in dendritic cell trafficking from the periphery to the inguinal lymph nodes and improved adaptive immune responses.</p>
</sec>
<sec id="sec004"><title>Conclusions</title>
<p>LNT decreases pathological changes of lymphedema and was shown to potently induce lymphangiogenesis. Lymphatic vessels induced by LNT were abnormal in appearance, but were functional and able to transport antigen-presenting cells. Animals treated with LNT have an increased ability to mount T cell-mediated immune responses when sensitized to antigens in the affected hindlimb.</p>
</sec>
</div>
</front>
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<author><name sortKey="Brown, J" uniqKey="Brown J">J Brown</name>
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<author><name sortKey="Choi, Dk" uniqKey="Choi D">DK Choi</name>
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<author><name sortKey="Koh, Bi" uniqKey="Koh B">BI Koh</name>
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<author><name sortKey="Kim, M" uniqKey="Kim M">M Kim</name>
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<author><name sortKey="Suzuki, Hi" uniqKey="Suzuki H">HI Suzuki</name>
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<author><name sortKey="Kiyono, K" uniqKey="Kiyono K">K Kiyono</name>
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<author><name sortKey="Morishita, Y" uniqKey="Morishita Y">Y Morishita</name>
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<author><name sortKey="Watabe, T" uniqKey="Watabe T">T Watabe</name>
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<author><name sortKey="Gs G" uniqKey="Gs G">GS G</name>
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<author><name sortKey="R R" uniqKey="R R">R R</name>
</author>
<author><name sortKey="Ls L" uniqKey="Ls L">LS L</name>
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<author><name sortKey="Qiu, Ss" uniqKey="Qiu S">SS Qiu</name>
</author>
<author><name sortKey="Lopez Penha, T" uniqKey="Lopez Penha T">T Lopez Penha</name>
</author>
<author><name sortKey="Keuter, X" uniqKey="Keuter X">X Keuter</name>
</author>
<author><name sortKey="Piatkowski De Grzymala, A" uniqKey="Piatkowski De Grzymala A">A Piatkowski de Grzymala</name>
</author>
<author><name sortKey="Tuinder, S" uniqKey="Tuinder S">S Tuinder</name>
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</analytic>
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<li>Suède</li>
<li>Taïwan</li>
<li>États-Unis</li>
</country>
<region><li>Communauté de Madrid</li>
<li>East Middle Sweden</li>
<li>Svealand</li>
<li>État de New York</li>
</region>
<settlement><li>Madrid</li>
<li>Uppsala</li>
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<orgName><li>Université d'Uppsala</li>
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<tree><country name="États-Unis"><region name="État de New York"><name sortKey="Huang, Jung Ju" sort="Huang, Jung Ju" uniqKey="Huang J" first="Jung-Ju" last="Huang">Jung-Ju Huang</name>
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<name sortKey="Garcia Nores, Gabriela D" sort="Garcia Nores, Gabriela D" uniqKey="Garcia Nores G" first="Gabriela D." last="García Nores">Gabriela D. García Nores</name>
<name sortKey="Gardenier, Jason C" sort="Gardenier, Jason C" uniqKey="Gardenier J" first="Jason C." last="Gardenier">Jason C. Gardenier</name>
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<name sortKey="Kataru, Raghu P" sort="Kataru, Raghu P" uniqKey="Kataru R" first="Raghu P." last="Kataru">Raghu P. Kataru</name>
<name sortKey="Ly, Catherine L" sort="Ly, Catherine L" uniqKey="Ly C" first="Catherine L." last="Ly">Catherine L. Ly</name>
<name sortKey="Mehrara, Babak J" sort="Mehrara, Babak J" uniqKey="Mehrara B" first="Babak J." last="Mehrara">Babak J. Mehrara</name>
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<country name="Taïwan"><noRegion><name sortKey="Huang, Jung Ju" sort="Huang, Jung Ju" uniqKey="Huang J" first="Jung-Ju" last="Huang">Jung-Ju Huang</name>
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</country>
<country name="Suède"><region name="Svealand"><name sortKey="Martinez Corral, Ines" sort="Martinez Corral, Ines" uniqKey="Martinez Corral I" first="Inés" last="Martínez-Corral">Inés Martínez-Corral</name>
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<country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Ortega, Sagrario" sort="Ortega, Sagrario" uniqKey="Ortega S" first="Sagrario" last="Ortega">Sagrario Ortega</name>
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