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Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node

Lymph node (LN) lipomatosis is a common but rarely discussed phenomenon associated with aging that involves a gradual exchange of the LN parenchyma into adipose tissue. The mechanisms behind these changes and the effects on the LN are unknown. We show that LN lipomatosis starts in the medullary regi...

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Autores principales: Bekkhus, Tove, Olofsson, Anna, Sun, Ying, Magnusson, Peetra U, Ulvmar, Maria H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108032/
https://www.ncbi.nlm.nih.gov/pubmed/36367235
http://dx.doi.org/10.1002/path.6030
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author Bekkhus, Tove
Olofsson, Anna
Sun, Ying
Magnusson, Peetra U
Ulvmar, Maria H
author_facet Bekkhus, Tove
Olofsson, Anna
Sun, Ying
Magnusson, Peetra U
Ulvmar, Maria H
author_sort Bekkhus, Tove
collection PubMed
description Lymph node (LN) lipomatosis is a common but rarely discussed phenomenon associated with aging that involves a gradual exchange of the LN parenchyma into adipose tissue. The mechanisms behind these changes and the effects on the LN are unknown. We show that LN lipomatosis starts in the medullary regions of the human LN and link the initiation of lipomatosis to transdifferentiation of LN fibroblasts into adipocytes. The latter is associated with a downregulation of lymphotoxin beta expression. We also show that isolated medullary and CD34(+) fibroblasts, in contrast to the reticular cells of the T‐cell zone, display an inherently higher sensitivity for adipogenesis. Progression of lipomatosis leads to a gradual loss of the medullary lymphatic network, but at later stages, collecting‐like lymphatic vessels are found inside the adipose tissue. The stromal dysregulation includes a dramatic remodeling and dilation of the high endothelial venules associated with reduced density of naïve T‐cells. Abnormal clustering of plasma cells is also observed. Thus, LN lipomatosis causes widespread stromal dysfunction with consequences for the immune contexture of the human LN. Our data warrant an increased awareness of LN lipomatosis as a factor contributing to decreased immune functions in the elderly and in disease. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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spelling pubmed-101080322023-04-18 Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node Bekkhus, Tove Olofsson, Anna Sun, Ying Magnusson, Peetra U Ulvmar, Maria H J Pathol Original Articles Lymph node (LN) lipomatosis is a common but rarely discussed phenomenon associated with aging that involves a gradual exchange of the LN parenchyma into adipose tissue. The mechanisms behind these changes and the effects on the LN are unknown. We show that LN lipomatosis starts in the medullary regions of the human LN and link the initiation of lipomatosis to transdifferentiation of LN fibroblasts into adipocytes. The latter is associated with a downregulation of lymphotoxin beta expression. We also show that isolated medullary and CD34(+) fibroblasts, in contrast to the reticular cells of the T‐cell zone, display an inherently higher sensitivity for adipogenesis. Progression of lipomatosis leads to a gradual loss of the medullary lymphatic network, but at later stages, collecting‐like lymphatic vessels are found inside the adipose tissue. The stromal dysregulation includes a dramatic remodeling and dilation of the high endothelial venules associated with reduced density of naïve T‐cells. Abnormal clustering of plasma cells is also observed. Thus, LN lipomatosis causes widespread stromal dysfunction with consequences for the immune contexture of the human LN. Our data warrant an increased awareness of LN lipomatosis as a factor contributing to decreased immune functions in the elderly and in disease. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. John Wiley & Sons, Ltd 2022-12-21 2023-03 /pmc/articles/PMC10108032/ /pubmed/36367235 http://dx.doi.org/10.1002/path.6030 Text en © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Bekkhus, Tove
Olofsson, Anna
Sun, Ying
Magnusson, Peetra U
Ulvmar, Maria H
Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node
title Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node
title_full Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node
title_fullStr Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node
title_full_unstemmed Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node
title_short Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node
title_sort stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108032/
https://www.ncbi.nlm.nih.gov/pubmed/36367235
http://dx.doi.org/10.1002/path.6030
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