Involvement of CXCL12/CXCR4 pair in migration of thymocytes from lactating mice

Abstract

During the postpartum and lactation period, the involuted thymus, affected by pregnancy hormones, initiates its morphophysiological recovery with the positive regulation of the hormone prolactin (PRL), present at high levels during lactation. PRL has pleiotropic effects on thymic epithelial cells, thymocytes, as well as on elements of the extracellular matrix. In this study, we evaluated the production of the chemokine CXCL12 by the thymic microenvironment and its receptor, CXCR4, by thymocytes from lactating female mice. To achieve this objective, we used C57BL/6 female mice that were nulliparous or on the 15th day of lactation. After euthanasia, their thymi were collected, weighed, and processed for histological analyses and PRL quantitation. In other experiments, the thymus was mechanically disrupted to obtain fresh thymocytes, which were subsequently subjected to in vitro assays and flow cytometry analyses. Also, the plasma serum of the females was collected to measure PRL levels. It was observed that there was lower cellularity and thymic weight on the 15th day of lactation, along with histological alterations that this organ normally exhibits during this period. It was found that the thymic supernatant presented higher levels of PRL than the animals' serum. Additionally, the thymic medulla exhibited higher quantities of CXCL12, and thymocytes displayed elevated levels of CXCR4, making them more adept at migrating in response to this chemotactic stimulus. Remarkably, this is the first report, to the best of our knowledge, indicating the action of the CXCL12/CXCR4 pair in the thymus during the physiological lactation period.

Keywords: Cell migration; Lactation; Prolactin; Thymic epithelial cell; Thymocyte; Thymus.