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Blood and tissue eosinophilia are associated with a number of infectious and inflammatory diseases. Corticosteroids are effective in reducing eosinophil numbers, but patients often develop resistance and toxic side effects from this non-specific treatment.
Exciting new roles for eosinophils have been discovered in regulating local immune responses and supporting specialized niches. Therefore, treatments that specifically target eosinophils are likely to be effective in modulating a number of prevalent diseases in allergy, autoimmunity and malignancy.
There is a growing need for development of safe and effective therapies that specifically target eosinophils. The aim of our research is to identify novel therapeutic targets to block eosinophil production and prevent the release of mature eosinophils from the bone marrow.
Eosinophils, like all blood cells, are produced in the bone marrow from hematopoietic stem cells (HSC). The common myeloid progenitor (CMP) is derived from HSCs and gives rise to all myeloid lineages, including eosinophils. Eosinophil lineage-committed progenitors (EoP) differentiate exclusively into fully mature eosinophils whereas granulocyte-monocyte progenitors (GMP) differentiate into neutrophils and monocytes/macrophages. Studies focused on understanding EoP biology may reveal new therapeutic targets for specifically regulating eosinophil production in the bone marrow.
Human eosinophils purified from donated blood.
Eosinophils are bone marrow-derived leukocytes that are normally less than 5% of leukocytes in the blood. Eosinophilia, a greater than normal number of eosinophils in the blood and/or tissues, can occur in variety of disorders, including parasitic infections, allergic diseases and adverse drug reactions. In addition, important new roles for eosinophils have been demonstrated in regulating local immune responses and specialized microenvironments. This suggests that therapy aimed at eosinophils may aid in controlling diseases not previously associated with eosinophils, such as autoimmunity and malignancy. We utilize cells, such as eosinophils purified from human blood donated for research (pink cells pictured above, H&E stain), to further our understanding of eosinophil development and effector functions with the aim to identify novel targets for eosinophil-directed therapies.
The Fulkerson Lab works closely with the Cincinnati Center for Eosinophilic Disorders, which brings together experts in allergy/immunology, gastroenterology, social work, nutrition and pathology to evaluate, treat and study eosinophilic disorders in children and adults.
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