Eosinophils have functions in health and in the pathogeneses of asthma, allergies and other diseases. Some roles of eosinophils are based on their acute, effector responses, such as their capacity to release preformed granule contents, including their distinctive granule cationic proteins. Other eosinophil functions are based on their regulated expression of cell surface receptors and ligands and their release of diverse cytokines that can mediate interactions with other cells in the microenvironment of tissue sites. Eosinophils function principally in tissue sites, especially submucosal sites, where eosinophils localize even in the absence of disease. For tissue-resident eosinophils, definitions of the interactions that occur between eosinophils and other immune cells in tissue sites are germane to understanding eosinophil functions in acute and chronic diseases. Amongst leukocytes, the structure of eosinophils is highly unique. Eosinophils in tissue sites of inflammation, such as asthmatic airways, characteristically exhibit ultrastructural alterations indicative of distinct intracellular mechanisms governing their functional responses. Mechanisms of vesicular transport underlie a unique eosinophil """"""""degranulation"""""""" process that selectively releases only certain specific granule proteins; but these mechanisms have never been defined. Eosinophils are cellular sources of multiple cytokines which notably are stored preformed in intracellular sites, including specific granules; but mechanisms regulating such release of eosinophil-derived cytokines are unknown. Likewise, some relevant immunologic proteins, such as CD40, are abundantly present preformed in intracellular pools within eosinophils; but mechanisms underlying the regulated expression of such proteins have not been defined. Our studies will investigate aspects of the functioning of eosinophils that relate the unique structural cell biology of eosinophils to their distinct functional roles in immune homeostasis and pathology. We will investigate intracellular mechanisms involved in the regulated release and/or expression of eosinophil-derived proteins, including cytokines and cell-surface ligands/receptors. The overall hypothesis is that functional responses of eosinophils in immunologic and other diseases are dependent on intracellular compartmentalization of eosinophil proteins and governed by specific intracellular signaling and trafficking mechanisms that differentially regulate the expression of these eosinophil proteins. Understanding the molecular and cellular mechanisms that regulate the extracellular release of eosinophil granule-stored cytokines and expression of other proteins will provide novel insights into eosinophil functions that involve interactions between eosinophils and other cells in tissue sites.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Lung Biology and Pathology Study Section (LBPA)
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Plaut, Marshall
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Beth Israel Deaconess Medical Center
United States
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Shamri, Revital; Young, Kristen M; Weller, Peter F (2018) Rho and Rac, but not ROCK, are required for secretion of human and mouse eosinophil-associated RNases. Clin Exp Allergy :
Weller, Peter F; Spencer, Lisa A (2017) Functions of tissue-resident eosinophils. Nat Rev Immunol 17:746-760
Wechsler, Michael E; Akuthota, Praveen; Jayne, David et al. (2017) Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med 376:1921-1932
Bandeira-Melo, Christianne; Paiva, Ligia Almeida; Amorim, Natália R T et al. (2017) EicosaCell: An Imaging-Based Assay to Identify Spatiotemporal Eicosanoid Synthesis. Methods Mol Biol 1554:127-141
Wang, H-B; Akuthota, P; Kanaoka, Y et al. (2017) Airway eosinophil migration into lymph nodes in mice depends on leukotriene C4. Allergy 72:927-936
Tucker, Joseph D; Hughes, Molly A; Durvasula, Ravi V et al. (2017) Measuring Success in Global Health Training: Data From 14 Years of a Postdoctoral Fellowship in Infectious Diseases and Tropical Medicine. Clin Infect Dis 64:1768-1772
Carmo, Lívia A S; Bonjour, Kennedy; Ueki, Shigeharu et al. (2016) CD63 is tightly associated with intracellular, secretory events chaperoning piecemeal degranulation and compound exocytosis in human eosinophils. J Leukoc Biol 100:391-401
Bettigole, Sarah E; Lis, Raphael; Adoro, Stanley et al. (2015) The transcription factor XBP1 is selectively required for eosinophil differentiation. Nat Immunol 16:829-37
Carmo, Lívia A S; Dias, Felipe F; Malta, Kássia K et al. (2015) Expression and subcellular localization of the Qa-SNARE syntaxin17 in human eosinophils. Exp Cell Res 337:129-135
Melo, Rossana C N; Weller, Peter F (2014) Unraveling the complexity of lipid body organelles in human eosinophils. J Leukoc Biol 96:703-12

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