PMN-MDSC in newborns: Regulation of the regulators

PMN-MDSC are pathologically activated neutrophils that acquire T cell (and NK cell) suppressive activity and thus function as negative regulators of effector lymphocytes in many disease conditions.^[1] For many years, these PMN-MDSC have mainly been seen as contributors to disease progression and severity, best exemplified in the context of cancer. However, more recently, PMN-MDSC have also been described in newborn mice and humans.^[2] This finding raised the question on the potential functional roles of these regulatory myeloid cells in neonate immunobiology. During the first days (mice) or weeks (human) of life, an initial seeding of microbiota in the gut takes place. The appearance of these microbiota triggers immune responses that could potentially lead to harmful inflammation and immunopathology. In this early phase of life, PMN-MDSC could be beneficial by limiting overshooting immune responses. Indeed, a recent paper by He et al.^[3] describes the transient presence of PMN-MDSC during the first month of life. Such PMN-MDSC have been shown to suppress T cells in a contact-depended manner, but the mechanism behind the transitory nature of this phenomenon has not yet been elucidated. In this issue of the Journal of Leukocyte Biology Perego et al. describe molecular mechanisms that regulate this transient increase and subsequent decrease of PMN-MDSC in newborn mice.^[4].