Abstract
During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcriptomic changes in TECs during the postpartum period in order to identify mechanisms triggering postpartum thymic regeneration. In particular, we performed flow cytometry analyses and deep RNA-sequencing on purified TEC subsets at several time points before and after parturition. We report that pregnancy-induced involution is not caused by loss of TECs since their number does not change during or after pregnancy. However, during pregnancy, we observed a significant depletion of all thymocyte subsets downstream of the double-negative 1 (DN1) differentiation stage. Variations in thymocyte numbers correlated with conspicuous changes in the transcriptome of cortical TECs (cTECs). The transcriptomic changes affected predominantly cTEC expression of Foxn1, its targets and several genes that are essential for thymopoiesis. By contrast, medullary TECs (mTECs) showed very little transcriptomic changes in the early postpartum regenerative phase, but seemed to respond to the expansion of single-positive (SP) thymocytes in the late phase of regeneration. Together, these results show that postpartum thymic regeneration is orchestrated by variations in expression of a well-defined subset of cTEC genes, that occur very early after parturition.
Highlights
Thymic involution that occurs during pregnancy is characterized by an important decrease in thymic mass and cellularity
We show that pregnancy-induced thymic involution is not associated with cell loss in the thymic epithelium, and that postpartum thymic regeneration is orchestrated by transcriptomic and phenotypic changes occurring primarily in cortical thymic epithelial cells (TECs)
To understand the factors involved in postpartum thymic regeneration, we studied lymphocyte and epithelial cell populations in the first month following parturition
Summary
Thymic involution that occurs during pregnancy is characterized by an important decrease in thymic mass and cellularity. This decrease affects all thymocyte subpopulations, including CD4−CD8− double negative (DNs), CD4+CD8+ double positive (DP) and single positive (SP) CD4+ and CD8+ thymocytes [1, 2]. This phenomenon of acute thymic involution is not caused by massive apoptosis of DP thymocytes, as found following sublethal irradiation or dexamethasone administration, but rather through a pause in thymocyte differentiation and proliferation [1]. Failure to regain immunocompetence would jeopardize survival of both females and their progeny [4]
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