Allergy and Clinical Immunology

Eosinophils are multifunctional leukocytes with diverse functions in health and disease. We first time demonstrate that IL-18 has a critical role in the development and maturation of eosinophils. Herein, we provide evidence that IL-18 differentiates eosinophils, even in the absence of endogenous IL-5, both ex vivo and under physiological conditions in vivo. IL-18 and IL-5 differentiated ex vivo eosinophils have differences in size, shape, granularity and differentially regulated CD274 (PDL1) transcript expression IL-18 activates B cells and subsets of specific T cells to produce IgE and eosinophil responsive cytokines including IL-5 and IL-13 to promote eosinophil influx into the tissues in experimental and human allergic diseases. IL-5 is an established factor for the rapid differentiation, expansion and survival of eosinophils. Eosinophils play a role in expelling gastrointestinal parasites in health and are involved in the pathogenesis of allergic states and allograft rejection. This distinct function of eosinophils is not yet not fully understood. The study provides a new understanding of eosinophil biology through the recognition of IL-18 differentiated CD274 (PDL1) expressing mature eosinophils that is detected even in blood of healthy individuals and allergic patients. Most importantly, it has been found that PDL1 expressing eosinophils are increased in the blood of asthma patients and solely accumulated in the tissue under allergic conditions. Activated epithelial cells and antigen presenting cells are the major source of induced IL-18 in allergic diseases. Our ex vivo and in vivo data provide evidence that implicates IL-18 in the development and maturation of pathogenic PDL1 expressing eosinophils. In brief, the analysis of mouse and human eosinophil in healthy and disease state indicates that IL-18 and IL-5 synergistically promote differentiation, maturation and proliferation of PDL1 expressing pathogenic eosinophils in allergic disease states. Collectively, first time identified the role of IL-18 in transforming naive eosinophils to pathogenic PDL1 expressing eosinophils and this finding may have broad implications regarding non-invasive diagnostic and therapeutic strategies for eosinophil-associated diseases.