Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis

Stephen P. Matthews, Sarah J. McMillan, Jeff D. Colbert, Rachel A. Lawrence, Colin Watts (Lead / Corresponding author)

Research output: Contribution to journalArticle

21 Citations (Scopus)
176 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)795-806
Number of pages12
JournalImmunity
Volume44
Issue number4
Early online date5 Apr 2016
DOIs
Publication statusPublished - 19 Apr 2016

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