Emily Mackey1,2 and Adam J. Moeser1 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48864, USA 2Comparative Biomedical Sciences Program, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina 27603, USA Correspondence: moeseradmsu.edu

Mast cells are critical innate immune effectors located throughout the body that are crucial for host defense mechanisms via orchestrating immune responses to a variety of host and environmental stimuli necessary for survival. The role of mast cells in brain development and behavior, meningeal function, and stress-related disorders has also been increasingly recognized. While critical for survival and development, excessive mast cell activation has been linked with an increasing number of inflammatory, stress-associated, and neuroimmune disorders including allergy/anaphylaxis, autoimmune diseases, migraine headache, and chronic pain disorders. Further, a strong sex bias exists for mast cell–associated diseases with females often at increased risk. Here we review sex differences in human mast cell–associated diseases and animal models, and the underlying biological mechanisms driving these sex differences, which include adult gonadal sex hormones as well the emerging organizational role of perinatal gonadal hormones on mast cell activity and development.