Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis.

Stephen P Matthews, Sarah J McMillan, Jeff D Colbert, Rachel A Lawrence, Colin Watts

Immunity 2016 Apr 19

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Eosinophils are now recognized as multifunctional leukocytes that provide critical homeostatic signals to maintain other immune cells and aid tissue repair. Paradoxically, eosinophils also express an armory of granule-localized toxins and hydrolases believed to contribute to pathology in inflammatory disease. How eosinophils deliver their supporting functions while avoiding self-inflicted injury is poorly understood. We have demonstrated that cystatin F (CF) is a critical survival factor for eosinophils. Eosinophils from CF null mice had reduced lifespan, reduced granularity, and disturbed granule morphology. In vitro, cysteine protease inhibitors restored granularity, demonstrating that control of cysteine protease activity by CF is critical for normal eosinophil development. CF null mice showed reduced pulmonary pathology in a model of allergic lung inflammation but also reduced ability to combat infection by the nematode Brugia malayi. These data identify CF as a "cytoprotectant" that promotes eosinophil survival and function by ensuring granule integrity. VIDEO ABSTRACT. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Stephen P Matthews, Sarah J McMillan, Jeff D Colbert, Rachel A Lawrence, Colin Watts. Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis. Immunity. 2016 Apr 19;44(4):795-806