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 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+PPARγ2+), 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.
Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Larissa G P
LG
Langhi
Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Leonardo R
LR
Andrade
Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Marilia Kimie
MK
Shimabukuro
Department of Immunology, Erasmus University, Rotterdam, Netherlands.
Willem
W
van Ewijk
Department of Veterans Affairs, Medical Services, Veterans Affairs Medical Center, Washington, District of Columbia, United States of America.
Dennis D
DD
Taub
Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Radovan
R
Borojevic
Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Valeria
V
de Mello Coelho
D000367:Age Factors; D000818:Animals; D001343:Autophagy; D002450:Cell Communication; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D050356:Lipid Metabolism; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D010588:Phagosomes / Q000378:metabolism; D010641:Phenotype; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*