Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentially (original) (raw)

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Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School

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Boston, Massachusetts

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USA

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Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School

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Boston, Massachusetts

,

USA

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Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School

,

Boston, Massachusetts

,

USA

Laboratory of Inflammation, Instituto Oswaldo Cruz

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Fio Cruz, Rio de Janeiro

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Brazil

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Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School

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Boston, Massachusetts

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USA

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Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School

,

Boston, Massachusetts

,

USA

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,

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School

,

Boston, Massachusetts

,

USA

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Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School

,

Boston, Massachusetts

,

USA

Correspondence: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, E/CLS-9, Boston, MA 02215, USA. E-mail: pweller@bidmc.harvard.edu

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Received:

23 January 2008

Revision received:

02 September 2008

Accepted:

03 September 2008

Published:

07 October 2008

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Lisa A Spencer, Craig T Szela, Sandra A C Perez, Casey L Kirchhoffer, Josiane S Neves, Amy L Radke, Peter F Weller, Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentially, Journal of Leukocyte Biology, Volume 85, Issue 1, Jan 2009, Pages 117–123, https://doi.org/10.1189/jlb.0108058
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Abstract

Eosinophils are innate immune leukocytes implicated in the initiation and maintenance of type 2 immune responses, including asthma and allergy. The ability to store and rapidly secrete preformed cytokines distinguishes eosinophils from most lymphocytes, which must synthesize cytokine proteins prior to secretion and may be a factor in the apparent Th2 bias of eosinophils. Multiple studies confirm that human eosinophils from atopic or hypereosinophilic donors can secrete over 30 cytokines with a varying and often opposing immune-polarizing potential. However, it remains unclear whether all of these cytokines are constitutively preformed and available for rapid secretion from eosinophils in the circulation of healthy individuals or are restricted to eosinophils from atopic donors. Likewise, the relative concentrations of cytokines stored within eosinophils have not been studied. Here, we demonstrate that human blood eosinophils are not singularly outfitted with Th2-associated cytokines but rather, constitutively store a cache of cytokines with nominal Th1, Th2, and regulatory capacities, including IL-4, IL-13, IL-6, IL-10, IL-12, IFN-γ, and TNF-α. We demonstrate further rapid and differential release of each cytokine in response to specific stimuli. As agonists, strong Th1 and inflammatory cytokines elicited release of Th2-promoting IL-4 but not Th1-inducing IL-12. Moreover, a large quantity of IFN-γ was secreted in response to Th1, Th2, and inflammatory stimuli. Delineations of the multifarious nature of preformed eosinophil cytokines and the varied stimulus-dependent profiles of rapid cytokine secretion provide insights into the functions of human eosinophils in mediating inflammation and initiation of specific immunity.

© 2009 Society for Leukocyte Biology

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