Immunity
Volume 44, Issue 4, 19 April 2016, Pages 795-806
Journal home page for Immunity

Article
Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis

https://doi.org/10.1016/j.immuni.2016.03.003Get rights and content
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Highlights

  • Cystatin F is a novel survival factor for eosinophils

  • Regulation of protease activity is critical for normal eosinophil granule biogenesis

  • Parasite immunity and allergic lung pathology are reduced in cystatin F null mice

Summary

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.

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Present address: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01545, USA