Differential response of mouse thymic epithelial cell types to ionizing radiation-induced dna damage
Calvo-Asensio, Irene ; Barthlott, Thomas ; von Muenchow, Lilly ; Lowndes, Noel F. ; Ceredig, Rhodri
Calvo-Asensio, Irene
Barthlott, Thomas
von Muenchow, Lilly
Lowndes, Noel F.
Ceredig, Rhodri
Repository DOI
Publication Date
2017-04-13
Keywords
Type
Article
Downloads
Citation
Calvo-Asensio, Irene; Barthlott, Thomas; von Muenchow, Lilly; Lowndes, Noel F. Ceredig, Rhodri (2017). Differential response of mouse thymic epithelial cell types to ionizing radiation-induced dna damage. Frontiers in Immunology 8 ,
Abstract
Thymic epithelial cells (TECs) are the main components of the thymic stroma that support and control T-cell development. Preparative regimens using DNA-damaging agents, such as total body irradiation and/or chemotherapeutic drugs, that are necessary prior to bone marrow transplantation (BMT) have profound deleterious effects on the hematopoietic system, including the thymic stroma, which may be one of the main causes for the prolonged periods of T-cell deficiency and the inefficient T cell reconstitution that are common following BMT. The DNA damage response (DDR) is a complex signaling network that allows cells to respond to all sorts of genotoxic insults. Hypoxia is known to modulate the DDR and play a role affecting the survival capacity of different cell types. In this study, we have characterized in detail the DDR of cortical and medullary TEC lines and their response to ionizing radiation, as well as the effects of hypoxia on their DDR. Although both mTECs and cTECs display relatively high radio-resistance, mTEC cells have an increased survival capacity to ionizing radiation (IR)-induced DNA damage, and hypoxia specifically decreases the radio-resistance of mTECs by upregulating the expression of the pro-apoptotic factor Bim. Analysis of the expression of TEC functional factors by primary mouse TECs showed a marked decrease of highly important genes for TEC function and confirmed cTECs as the most affected cell type by IR. These findings have important implications for improving the outcomes of BMT and promoting successful T cell reconstitution.
Funder
Publisher
Frontiers Media SA
Publisher DOI
10.3389/fimmu.2017.00418
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland