Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous
Intrathymic lipid-laden multilocular cells (LLMC) are known to express pro-inflammatory factors that might regulate functional activity of the thymus. However, the phenotype of age-associated intrathymic LLMC is still controversial. In this study, we evaluated LLMC density in the aging thymus and be...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624951/ |
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pubmed-4624951 |
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pubmed-46249512015-11-06 Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous Langhi, Larissa G. P. Andrade, Leonardo R. Shimabukuro, Marilia Kimie van Ewijk, Willem Taub, Dennis D. Borojevic, Radovan de Mello Coelho, Valeria Research Article Intrathymic lipid-laden multilocular cells (LLMC) are known to express pro-inflammatory factors that might regulate functional activity of the thymus. However, the phenotype of age-associated intrathymic LLMC is still controversial. In this study, we evaluated LLMC density in the aging thymus and better characterized their distribution, ultrastructure and phenotype. Our results show an increased density of LLMC in the thymus from 03 to 24 months of age. Morphologically, intrathymic LLMC exhibit fibroblastoid fusiform, globular or stellate shapes and can be found in the subcapsular region as well as deeper in the parenchyma, including the perivascular area. Some parenchymal LLMC were like telocytes accumulating lipids. We identified lipid droplets with different electrondensities, lipofuscin granules and autolipophagosome-like structures, indicating heterogeneous lipid content in these cells. Autophagosome formation in intrathymic LLMC was confirmed by positive staining for beclin-1 and perilipin (PLIN), marker for lipid droplet-associated proteins. We also found LLMC in close apposition to thymic stromal cells, endothelial cells, mast cells and lymphocytes. Phenotypically, we identified intrathymic LLMC as preadipocytes (PLIN+PPARĪ³2+), brown adipocytes (PLIN+UCP1+), macrophages (PLIN+Iba-1+) or pericytes (PLIN+NG2+) but not epithelial cells (PLIN- panCK+). These data indicate that intrathymic LLMC are already present in the young thymus and their density significantly increases with age. We also suggest that LLMC, which are morphologically distinct, establish direct contact with lymphocytes and interact with stromal cells. Finally, we evidence that intrathymic LLMC correspond to not only one but to distinct cell types accumulating lipids. Public Library of Science 2015-10-28 /pmc/articles/PMC4624951/ /pubmed/26509710 http://dx.doi.org/10.1371/journal.pone.0141516 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Langhi, Larissa G. P. Andrade, Leonardo R. Shimabukuro, Marilia Kimie van Ewijk, Willem Taub, Dennis D. Borojevic, Radovan de Mello Coelho, Valeria |
| spellingShingle |
Langhi, Larissa G. P. Andrade, Leonardo R. Shimabukuro, Marilia Kimie van Ewijk, Willem Taub, Dennis D. Borojevic, Radovan de Mello Coelho, Valeria Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous |
| author_facet |
Langhi, Larissa G. P. Andrade, Leonardo R. Shimabukuro, Marilia Kimie van Ewijk, Willem Taub, Dennis D. Borojevic, Radovan de Mello Coelho, Valeria |
| author_sort |
Langhi, Larissa G. P. |
| title |
Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous |
| title_short |
Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous |
| title_full |
Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous |
| title_fullStr |
Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous |
| title_full_unstemmed |
Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous |
| title_sort |
lipid-laden multilocular cells in the aging thymus are phenotypically heterogeneous |
| description |
Intrathymic lipid-laden multilocular cells (LLMC) are known to express pro-inflammatory factors that might regulate functional activity of the thymus. However, the phenotype of age-associated intrathymic LLMC is still controversial. In this study, we evaluated LLMC density in the aging thymus and better characterized their distribution, ultrastructure and phenotype. Our results show an increased density of LLMC in the thymus from 03 to 24 months of age. Morphologically, intrathymic LLMC exhibit fibroblastoid fusiform, globular or stellate shapes and can be found in the subcapsular region as well as deeper in the parenchyma, including the perivascular area. Some parenchymal LLMC were like telocytes accumulating lipids. We identified lipid droplets with different electrondensities, lipofuscin granules and autolipophagosome-like structures, indicating heterogeneous lipid content in these cells. Autophagosome formation in intrathymic LLMC was confirmed by positive staining for beclin-1 and perilipin (PLIN), marker for lipid droplet-associated proteins. We also found LLMC in close apposition to thymic stromal cells, endothelial cells, mast cells and lymphocytes. Phenotypically, we identified intrathymic LLMC as preadipocytes (PLIN+PPARĪ³2+), brown adipocytes (PLIN+UCP1+), macrophages (PLIN+Iba-1+) or pericytes (PLIN+NG2+) but not epithelial cells (PLIN- panCK+). These data indicate that intrathymic LLMC are already present in the young thymus and their density significantly increases with age. We also suggest that LLMC, which are morphologically distinct, establish direct contact with lymphocytes and interact with stromal cells. Finally, we evidence that intrathymic LLMC correspond to not only one but to distinct cell types accumulating lipids. |
| publisher |
Public Library of Science |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624951/ |
| _version_ |
1613494466692251648 |