Lipid-Laden Multilocular Cells in the Aging Thymus Are Phenotypically Heterogeneous

PLoS One. 2015 Oct 28;10(10):e0141516. doi: 10.1371/journal.pone.0141516. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Autophagy
  • Cell Communication
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Female
  • Lipid Metabolism*
  • Lymphocytes / cytology
  • Lymphocytes / metabolism
  • Mast Cells / cytology
  • Mast Cells / metabolism
  • Mice
  • Phagosomes / metabolism
  • Phenotype*
  • Stromal Cells / cytology
  • Stromal Cells / metabolism
  • Thymocytes / cytology
  • Thymocytes / metabolism
  • Thymus Gland / cytology*
  • Thymus Gland / metabolism*

Grants and funding

This work was supported by the Rio de Janeiro State Funding Agency/FAPERJ http://www.faperj.br/ Grant # 110.953/2013 to VMC, and National Council of Technological and Scientific Development/CNPq http://www.cnpq.br/ Grant# 475360/2010-9 to VMC.