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Chapter 14 : The Regulatory Function of Eosinophils

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Abstract:

Eosinophils represent a minor component of circulating leukocytes and are generally considered to be terminally differentiated as postmitotic cells, yet it is now appreciated that they can be long-lived, multifaceted granulocytes involved in a variety of regulatory functions. Like other granulocytes, eosinophils develop and differentiate in the bone marrow. Under homeostasis, eosinophils are distributed in the blood, lung, thymus, uterus, adipose tissues, mammary gland, spleen and the lamina propria of the gastrointestinal (GI) tract ( ), indicating a physiological function in each organ. Although eosinophils outside of the bone marrow are deemed as mature, recent evidence suggests the existence of multiple tissue-specific subtypes on the basis of distinct cell surface marker expression and functions ( ). Driven by eosinophil-specific chemokines (primarily eotaxins) produced at baseline and markedly upregulated after a variety of stimuli ( ), mature eosinophils are recruited from the circulation into their physiological locations and inflammatory sites, respectively. The cytokine interleukin-5 (IL-5), produced primarily by type 2 T helper (Th2) cells ( ) and type 2 innate helper lymphoid cells (ILC2) ( ), is crucial for eosinophil differentiation, priming, and survival ( ). Conversely, eosinophils also serve as a source of a variety of cytokines and growth factors closely associated with multiple immunomodulatory functions to be discussed later. Through their vast cytokine arsenal and engagement of cell contact, eosinophils modulate immune responses through an array of interactive and orchestrated mechanisms, in and fashions, by cellular and humoral mediators, in both innate and adaptive immune responses. Recently, a burgeoning body of evidence has uncovered several underappreciated roles for eosinophils that could modulate both the adaptive and innate arms of immunity. An essential goal of this chapter is to summarize the role of eosinophils in physiological and inflammatory processes in human and small mammal models in order to identify novel pharmacological targets for specific disease management.

Citation: Wen T, Rothenberg M. 2017. The Regulatory Function of Eosinophils, p 257-269. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0020-2015
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Figure 1

Schematic summary of eosinophil-tropic signaling and eosinophil cellular and humoral regulatory functions. EOS, eosinophils; Mast, mast cells; Epi, epithelium; ADCC, antibody-dependent cell-mediated cytotoxicity; Ag, antigen; PMN, polymorphonuclear leukocyte (neutrophil).

Citation: Wen T, Rothenberg M. 2017. The Regulatory Function of Eosinophils, p 257-269. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0020-2015
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Image of Figure 2
Figure 2

Research tool summary and questions to be answered. Although recent advances provide tremendous insight into the regulatory functions of eosinophils, important questions remain. With the increasing number of tools available (upper panel), progress in the listed areas (lower panel, blue boxes), in the context of key eosinophil regulation elements (ovals), will be interesting and crucial to understanding the still enigmatic function of eosinophils. EOS, eosinophils; EPO-DT, EPO-driven diphtheria toxin expression mice; EMT, epithelial-mesenchymal transition; miR, microRNA; GOI, gene of interest; Tg, transgenic; (D) KO, (double) knockout; APCs, antigen-presenting cells. Gene EPX encodes the protein product of eosinophil peroxidase (EPO).

Citation: Wen T, Rothenberg M. 2017. The Regulatory Function of Eosinophils, p 257-269. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0020-2015
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