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Pathogenic Advances and Therapeutic Perspectives for Eosinophilic Inflammation

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With the recent approval of the first eosinophil-depleting therapeutic agent for treatment of severe eosinophilic asthma, eosinophils and eosinophilic disorders are in the limelight. The slow but determined development of this monoclonal antibody directed against interleukin-5, the major eosinophilopoietic ...

With the recent approval of the first eosinophil-depleting therapeutic agent for treatment of severe eosinophilic asthma, eosinophils and eosinophilic disorders are in the limelight. The slow but determined development of this monoclonal antibody directed against interleukin-5, the major eosinophilopoietic factor, illustrates how efforts to break down a heterogeneous human disease into clinical and/or mechanistic subsets can be rewarding and can translate into major improvements in patient management and outcome. This process has also highlighted how careful post-hoc assessment of clinical trial results can result in a better understanding of pathogenic mechanisms underlying specific aspects of the disease under study, resulting in improved design of subsequent studies, and ultimately, approval of new drugs.

However, it is increasingly clear that complex disorders involving eosinophils such as asthma and atopic dermatitis are the final outcome of complex interactions between diverse cell types and mediators, beyond eosinophils and IL-5. These include type 2 helper T cells and innate lymphoid cells, mast cells, and a variety of factors that either activate these cells or are released by them. Efforts towards understanding pathogenic mechanisms of clinical conditions associated with eosinophilia have intensified, to better delineate which of these actors represent the most meaningful targets for innovative therapeutic agents. Although a considerable amount of research has focused on asthma because it is a common condition, and because management of severe asthma remains a major challenge, knowledge of the genetic and environmental factors and pathogenic mechanisms underlying its phenotypic heterogeneity remains lacunary and fragmented. Several rare eosinophilic disorders with more homogenous features have proven to be extremely useful models to reach a better understanding of the involvement of eosinophils in tissue damage and dysfunction, and of the microenvironmental interactions operating within the complex network of eosinophilic inflammation. Unraveling this interplay has resulted in advances in the development of molecular tools to detect disease subsets and to monitor therapeutic responses, and in identification of promising new therapeutic targets. Precision medicine for management of eosinophilic disorders has now become a realistic endeavor.

This Research Topic dedicated to eosinophilic conditions covers aspects of the biology of eosinophils and closely related cells of particular relevance for drug development, reports on translational research investigating pathogenic mechanisms of specific eosinophilic disorders in humans that will likely result in significant changes in the way patients are managed, and presents an overview of the current advancement of targeted drug development for these conditions, with a special focus on asthma.


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