Dissecting the Mechanisms of Innate Defense in the Lungs during Lactation

Abstract

During reproduction, the maternal immune system undergoes several changes to accommodate both the semi-allogeneic fetus and the metabolic shifts associated with breast milk production. While these changes have been studied in the blood and placenta during pregnancy, shifts in the barrier tissues, which are frequently exposed to environmental insults, have not been as well studied. Further, how the immune system changes in these tissues during the lactation period is not known. Recently, our lab has found a specific increase in neutrophils within the pulmonary endothelium and bone marrow during lactation. The margination process in the lung is due to secretion of neutrophil chemokines by the vascular endothelium; however, the mechanism for increased proliferation in the bone marrow is still unknown. Furthermore, the lab has found upregulation of innate defense-related genes within the lung epithelium during lactation, as well as upregulation of thyroid hormone-associated genes. The mechanism behind this enhanced defense, as well as possible contribution from thyroid hormones, remains unknown. This thesis aims to characterize the broad mechanisms underlying these immune adaptations by investigating the role of two hormones, prolactin and thyroid hormone during lactation. Analysis of these two pathways reveals limited direct evidence for prolactin impacting increased neutrophil proliferation in the bone marrow or thyroid hormone in enhancing innate defense in the lung epithelium. The results of this thesis characterize mechanisms of immune change during lactation and provide enhanced understanding of maternal adaptation during reproduction.