The Immune System as a Novel Regulator of Sex Differences in Brain and Behavioral Development

Sexual differentiation of the brain occurs early in life as a result of sex-typical hormone action and sex chromosome effects. Immunocompetent cells are being recognized as underappreciated regulators of sex differences in brain and behavioral development, including microglia, astrocytes, and possibly other less well studied cell types, including T cells and mast cells. Immunocompetent cells in the brain are responsive to steroid hormones, but their role in sex-specific brain development is an emerging field of interest. This Review presents a summary of what is currently known about sex differences in the number, morphology, and signaling profile of immune cells in the developing brain and their role in the early-life programming of sex differences in brain and behavior. We review what is currently known about sex differences in the response to early-life perturbations, including stress, inflammation, diet, and environmental pollutants. We also discuss how and why understanding sex differences in the developing neuroimmune environment may provide insight into understanding the etiology of several neurodevelopmental disorders. This Review also highlights what remains to be discovered in this emerging field of developmental neuroimmunology and underscores the importance of filling in these knowledge gaps. (C) 2016 Wiley Periodicals, Inc.