title: Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis.
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.
authors.affiliation: Division of Cell Signaling & Immunology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Matthews
authors.affiliation: Division of Cell Signaling & Immunology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: McMillan
authors.affiliation: Division of Cell Signaling & Immunology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Colbert
authors.affiliation: Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Lawrence
authors.affiliation: Division of Cell Signaling & Immunology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK. Electronic address: c.watts@dundee.ac.uk.
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
mesh_terms: D000818:Animals; D017178:Brugia malayi / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D015891:Cystatins / Q000235:genetics* / Q000276:immunology*; D057056:Cysteine Proteases / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology*; D005368:Filariasis / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology
chemical_list: D015891:Cystatins; C550521:cystatin F, mouse; D010047:Ovalbumin; D057056:Cysteine Proteases