Preface

Excerpt

In 1994, Pollard and Henninghausen reported the unexpected observation that mice genetically deficient in a cytokine called colony-stimulating factor 1 (CSF1) failed to lactate [1]. As this cytokine is essential for normal macrophage proliferation, differentiation, survival and motility, deficiency in CSF1 caused these mice to be largely devoid of resident tissue macrophages. Investigation of this defect demonstrated that macrophages regulate developmental processes in the mammary gland, such that the absence of macrophages perturbed branching morphogenesis during pregnancy and led to a failure of lactation. Until this time, macrophages were known as immune system cells involved in phagocytosis, the presentation of antigens to generate adaptive immune responses and as effector cells that assist in elimination of bacterial and viral infections. That paper, published in the Proceedings of the National Academy of Sciences USA, went largely unnoticed by mammary gland biologists until 1997, when Dr Pollard was invited to speak at a Jackson Labs meeting on “Animal models in breast cancer” (Pollard, personal communication). Further studies on CSF1-deficient mice demonstrated the significance of macrophages in mammary branching morphogenesis, and finally led to widespread acceptance of the critical role these immune system cells play in normal mammary gland development. These discoveries eventually became a paradigm for the developmental roles of macrophages in other tissues, in regulating epithelial cell development and tissue complexity. …