Role of negative regulation of immune signaling pathways in neutrophil function.

Polymorphonuclear neutrophils (PMNs) play a critical role in host defense against infection and in the resolution of inflammation. However, immune responses mediated by PMN must be tightly regulated to facilitate elimination of invading pathogens without inducing detrimental inflammation and host tissue damage. Specific engagement of cell surface immunoreceptors by a diverse range of extracellular signals regulates PMN effector functions through differential activation of intracellular signaling cascades. Although mechanisms of PMN activation mediated via cell signaling pathways have been well described, less is known about negative regulation of PMN function by immune signaling cascades. Here, we provide an overview of immunoreceptor-mediated negative regulation of key PMN effector functions including maturation, migration, phagocytosis, reactive oxygen species release, degranulation, apoptosis, and NET formation. Increased understanding of mechanisms of suppression of PMN effector functions may point to possible future therapeutic targets for the amelioration of PMN-mediated autoimmune and inflammatory diseases. ©2017 Society for Leukocyte Biology.