C/EBPß deletion in macrophages impairs mammary gland alveolar budding during the estrous cycle.

Macrophages have important roles in mammary gland development and tissue homeostasis, but the specific mechanisms that regulate macrophage function need further elucidation. We have identified C/EBPß as an important transcription factor expressed by multiple macrophage populations in the normal mammary gland. Mammary glands from mice with C/EBPß-deficient macrophages (Cebpb ΔM) show a significant decrease in alveolar budding during the diestrus stage of the reproductive cycle, whereas branching morphogenesis remains unchanged. Defects in alveolar budding were found to be the result of both systemic hormones and local macrophage-directed signals. RNA sequencing shows significant changes in PR-responsive genes and alterations in the Wnt landscape of mammary epithelial cells of Cebpb ΔM mice, which regulate stem cell expansion during diestrus. Cebpb ΔM macrophages demonstrate a shift from a pro-inflammatory to a tissue-reparative phenotype, and exhibit increased phagocytic capacity as compared to WT. Finally, Cebpb ΔM macrophages down-regulate Notch2 and Notch3, which normally promote stem cell expansion during alveolar budding. These results suggest that C/EBPß is an important macrophage factor that facilitates macrophage-epithelial crosstalk during a key stage of mammary gland tissue homeostasis.

Emerging functions of C/EBPß in breast cancer.

Breast tumorigenesis relies on complex interactions between tumor cells and their surrounding microenvironment, orchestrated by tightly regulated transcriptional networks. C/EBPß is a key transcription factor that regulates the proliferation and differentiation of multiple cell types and modulates a variety of biological processes such as tissue homeostasis and the immune response. In addition, C/EBPß has well-established roles in mammary gland development, is overexpressed in breast cancer, and has tumor-promoting functions. In this review, we discuss context-specific roles of C/EBPß during breast tumorigenesis, isoform-specific gene regulation, and regulation of the tumor immune response. We present challenges in C/EBPß biology and discuss the importance of C/EBPß isoform-specific gene regulation in devising new therapeutic strategies.

Disgust and obsessive-compulsive disorder: an update.

In this paper, we review the growing body of literature investigating the association between obsessive-compulsive disorder (OCD) and the emotion of disgust. Initially studied with regard to specific phobias, the potential role of disgust responses in contamination concerns has led researchers to investigate possible associations between disgust and OCD symptoms. The literature on disgust-sensitivity in OCD is reviewed. Studies of disgust recognition in OCD and research using neuroimaging methods are then summarized. We suggest that disgust has a moderate association with OCD symptoms, particularly those which are contamination-based or which have a religious focus. Evidence for a disgust recognition deficit in patients with OCD is lacking; however, neuroimaging findings have confirmed hypothesized associations between contamination-focused OCD and the insula cortex, which has been implicated in disgust processing. Finally, treatment implications are discussed, and suggestions are made for further research.