Publications

Mast cells (MCs) are capable of executing powerful inflammatory response programs triggered by surface IgE cross-linking or through pattern recognition receptors. The question of how MCs contribute to human disease has been intensely investigated and stimulated much controversy. Correlative evidence comes from human studies, pointing to pathogenetic or protective MC functions in patients with atopic conditions, autoimmune disorders, type 2 diabetes, chronic urticaria, mastocytosis, and cancer. Experiments in MC-deficient mice underpinned key roles for MCs in patients with IgE-mediated allergic conditions. Important pathogenetic MC contributions to other inflammatory and neoplastic conditions were suggested by studies in traditional KIT mutant MC-deficient mouse strains. However, many of these findings were not reproduced in more recently developed improved mouse models of MC deficiency, largely ruling out roles for MCs in mouse models for autoimmune disease, diabetes, and cancer. We discuss limitations of studies in mice and human subjects and provide suggestions for how they can be overcome, such as through the development of specific and selective MC-targeted treatments. (J Allergy Clin Immunol 2019;144:S19-30.)