Studies will investigate capabilities and mechanisms whereby eosinophils, including those recruited within airways in asthma, function as antigen-presenting cells that are of importance in propagating or modulating varied lymphocyte-dependent responses to respiratory tract encountered antigens. As antigen-presenting cells, eosinophils have distinct capabilities: First, airway eosinophils express requisite Class II MHC and lymphocyte costimulatory proteins. Second, eosinophils, like dendritic cells, function as """"""""professional"""""""" antigen-presenting cells in expressing lymphocyte costimulatory proteins and activating unsensitized, naive T cells. Third, eosinophils, in contrast to other antigen-presenting cells, contain preformed stores of diverse cytokines that can be rapidly and selectively secreted to modulate varied lymphocyte responses. Fourth, eosinophils, like other antigen-presenting cells, utilize Fc receptor- mediated mechanisms to enhance antigen presentation by antigen-presenting cells. Eosinophil IgE, IgA and IgG receptors, together with airway allergen-specific IgE, IgA and IgG antibodies, can effectively present allergens. Fifth, airway eosinophils traffick into lymph nodes, spleen and even the thymus enabling airway antigens to be processed and transported into regional and systemic lymphoid tissues for presentation to varied lymphocytes. Sixth, eosinophils express ligands and receptors classically associated with dendritic cells, including DC-SIGN. Moreover, eosinophils can modulate B lymphocyte responses since eosinophils are critical participants in alum immunization-mediated B cell priming. Hypotheses to be tested are: that eosinophils trafficking from the airways are effective at presenting antigens to regulate, potentially differing, T lymphocyte responses in both regional and systemic lymphoid cells;that selective, restricted secretion of eosinophil cytokines mediates differential regulation of eosinophil antigen-presenting cell functions;and that eosinophils have roles in mediating the priming and responsiveness of B cells. Studies aim to investigate mechanisms by which eosinophils traffic and function as antigen-presenting cells to regulate regional and systemic T cell responses;eosinophil cytokines function in differential mediation of eosinophil antigen-presenting cell functions, and eosinophils function in B cell priming and activation. Roles for eosinophils as antigen-presenting cells in mediating allergic responses to airway antigens would provide novel insights into the characteristically chronic nature of asthma and other allergic airway diseases.

Public Health Relevance

. Asthma is an increasingly prevalent disease and a major public health problem. The research will help in understanding mechanisms that contribute to making asthma a chronic and persistent disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Lung Cellular, Molecular, and Immunobiology Study Section (LCMI)
Program Officer
Plaut, Marshall
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Beth Israel Deaconess Medical Center
United States
Zip Code
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 :
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
Ueki, Shigeharu; Tokunaga, Takahiro; Fujieda, Shigeharu et al. (2016) Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation. Curr Allergy Asthma Rep 16:54
Ueki, Shigeharu; Konno, Yasunori; Takeda, Masahide et al. (2016) Eosinophil extracellular trap cell death-derived DNA traps: Their presence in secretions and functional attributes. J Allergy Clin Immunol 137:258-267
Melo, Rossana C N; Weller, Peter F (2014) Unraveling the complexity of lipid body organelles in human eosinophils. J Leukoc Biol 96:703-12
Melo, Rossana C N; Morgan, Ellen; Monahan-Earley, Rita et al. (2014) Pre-embedding immunogold labeling to optimize protein localization at subcellular compartments and membrane microdomains of leukocytes. Nat Protoc 9:2382-94
Akuthota, Praveen; Capron, Kelsey; Weller, Peter F (2014) Eosinophil purification from peripheral blood. Methods Mol Biol 1178:13-20
Shamri, R; Young, K M; Weller, P F (2013) PI3K, ERK, p38 MAPK and integrins regulate CCR3-mediated secretion of mouse and human eosinophil-associated RNases. Allergy 68:880-9
Akuthota, Praveen; Ueki, Shigeharu; Estanislau, Jessica et al. (2013) Human eosinophils express functional CCR7. Am J Respir Cell Mol Biol 48:758-64
Ueki, Shigeharu; Melo, Rossana C N; Ghiran, Ionita et al. (2013) Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans. Blood 121:2074-83

Showing the most recent 10 out of 45 publications