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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2022
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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. |
format | Online Article Text |
id | pubmed-10108032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
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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