Alterations of Thymic Epithelial Cells in Lipopolysaccharide-induced Neonatal Thymus Involution

Abstract

Background: Vascular endothelial growth factor (VEGF) in the thymus was mainly produced by the thymic epithelial cells (TECs), the predominant component of the thymic microenvironment. The progression of TECs and the roles of VEGF in the neonatal thymus during sepsis have not been reported. This study aimed to explore the alterations of TECs and VEGF level in the neonatal thymus involution and to explore the possible mechanisms at the cellular level. Methods: By establishing a model of clinical sepsis, the changes of TECs were measured by hematoxylin-eosin staining, confocal microscopy, and flow cytometry. Moreover, the levels of VEGF in serum and thymus were assessed based on enzyme-linked immunosorbent assay and Western blotting. Results: The number of thymocytes and TECs was significantly decreased 24 h after lipopolysaccharide (LPS) challenge, (2.40 ± 0.46)×10 7 vs. (3.93 ± 0.66)×10 7 and (1.16 ± 0.14)×10 5 vs. (2.20 ± 0.19)×10 5 , P < 0.05, respectively. Cortical TECs and medullary TECs in the LPS-treated mice were decreased 1.5-fold and 3.9-fold, P < 0.05, respectively, lower than those in the controls. The number of thymic epithelial progenitors was also decreased. VEGF expression in TECs was down-regulated in a time-dependent manner. Conclusion: VEGF in thymic cells subsets might contribute to the development of TECs in neonatal sepsis.

Keywords

• Lipopolysaccharide; Thymic Epithelial Cells; Thymus Involution; Vascular Endothelial Growth Factor