Abstract
Abstract Age-related thymic involution is characterized by decreased thymopoiesis and increased white adipose tissue in the perivascular space. Previously, we described the presence of intrathymic lipid-laden multilocular cells (LLMC) expressing factors known to promote thymic atrophy. In this study, we aimed to characterize the distribution, morphology and phenotype of LLMC. Our results show that LLMC are distributed in thymic capsule, parenchyma and surrounding blood vessels and increase with aging. Based on their shape and/or location, LLMC present globular, fibroblastoid or pericyte-like morphology. Our ultrastructural analyses showed that LLMC contain lipid droplets with distinct electrondensities and autolipophagossome-like structures in their cytoplasm. In addition, we found LLMC interacting directly with lymphocytes, endothelial cells and mast cells in the thymic parenchyma. Furthermore, mast cells were quantified and increase in thymus with age. By immunohistochemistry, we analyzed the phenotype of LLMC and we found cells positively stained with specific markers for pericytes (α-SMA, NG2), macrophages (CD11b, F4/80), pre-adipocytes (PPARγ2) and brown adipocytes (UCP1) in the aging thymus. In conclusion, LLMC are not simply differentiating adipocytes, but correspond to distinct cellular populations, including macrophages and mesenchymal-derived cells that assume a lipid-laden morphology and are able of interacting with thymocytes and distinct thymic microenvironmental cells.
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