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EOSINOPHILOPOIESIS AT THE CROSS-ROADS OF RESEARCH ON DEVELOPMENT, IMMUNITY AND DRUG DISCOVERY
Affilliation
Universidade Federal do Rio de Janeiro. Deparment de Imunologia. Rio de Janeiro, RJ, Brasil.
Fundação. Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Pediatria. Rio de Janeiro, RJ, Brasil.
Fundação. Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Pediatria. Rio de Janeiro, RJ, Brasil.
Abstract
Eosinophils are a minority subpopulation of leukocytes whose roles in host defense against infection remain
controversial, but which have been implicated in the pathogenesis of both acute allergic inflammation and the chronic
bronchopulmonary remodelling in asthma. Eosinophilia, a hallmark of both helminth infections and atopic diseases, is maintained
through upregulation of eosinophilopoiesis by means of increased production and effectiveness of Interleukin-5 (IL-5), a major
Th2 cytokine. These mechanisms are further modulated by a wide variety of agents, including glucocorticoids, nonsteroidal anti-inflammatory drugs and mediators of inflammation. We review recent progress made by different groups in the study of
eosinophilopoiesis that led to the identification of the heterogeneous targets for developmental regulation by IL-5 and other
agents, and to the ongoing characterization of the molecular mechanisms that ensure their commitment to the eosinophil lineage.
We argue that the study of eosinophilopoiesis provides insight into basic developmental processes, and especially into how
modulators influence the constitutive rate of eosinophil production by controlling the rates of apoptosis and terminal
differentiation. The mechanisms underlying the apparently paradoxical effects of dexamethasone, a drug widely employed to
control inflammation, as well as the role of specific molecular targets (including inducible NO synthase and CD95/Fas) in
developmental regulation, are discussed in detail. We further argue that eosinophilopoiesis offers unique insights of how immune
and endocrine effector loops interact to control both the steady-state responses to IL-5 and the susceptibility to modulation of
these responses by drugs and cytokines. We also review the existing evidence on the recruitment of circulating stem cells and
progenitors into inflammatory sites, and on a critical role for IL-5 in the accumulation of eosinophil lineage-committed
progenitors in lungs of allergic mice. Finally, we review recent progress in the study of the regulatory T cell populations present
in bone-marrow, and discuss alternative mechanisms through which cellular immunity may influence eosinophilopoiesis.
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