Inhibitory receptors on eosinophils: a direct hit to a possible Achilles heel?

Since their discovery, much data have been accumulated on eosinophil differentiation, morphology, trafficking, and anatomical location(s) in health and disease. Although "classic" activation pathways (such as cytokines, chemokines, proinflammatory components, and adhesion molecules) regulating eosinophil activation have been widely explored, the presence of other activation molecules that might be disease specific is limited. Furthermore, the expression and function of inhibitory receptors on eosinophils have received scant attention. The need to identify new pathways that regulate eosinophil activation is a crucial goal as it can expand our knowledge on this peculiar cell and provide insights into important queries regarding the physiologic function of eosinophils. Over the past several years, it has become increasingly apparent that eosinophils express several receptors belonging to the immunoglobulin superfamily. In this review, we summarize the current knowledge on the expression and function of new pathways that govern eosinophil activation. In addition, we will propose some hypotheses regarding the ability to use these pathways as a future therapeutic approach. In conclusion, we assume that targeting inhibitory receptors on eosinophils may provide opportunities for immunoregulatory therapy in the near future.