Microvesicles released by apoptotic human neutrophils suppress proliferation and IL-2/IL-2 receptor expression of resting T helper cells

Membrane-coated microvesicles (MVs) have been identified as important mediators in intercellular communication. During the process of apoptosis, dying cells dynamically release MVs. Neutrophils are the most abundant type of leukocytes in the circulation. Due to their very short lifespan, it is likel...

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Main Authors: Shen, Guifen (Author) , Krienke, Stefan (Author) , Schiller, Petra (Author) , Nießen, Anna (Author) , Eckstein, Volker (Author) , Schiller, Martin (Author) , Lorenz, Hanns-Martin (Author) , Tykocinski, Lars-Oliver (Author)
Format: Article (Journal)
Language:English
Published: 10 March 2017
In: European journal of immunology
Year: 2017, Volume: 47, Issue: 5, Pages: 900-910
ISSN:1521-4141
DOI:10.1002/eji.201546203
Online Access:Verlag, Volltext: http://dx.doi.org/10.1002/eji.201546203
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.201546203
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Author Notes:Guifen Shen, Stefan Krienke, Petra Schiller, Anna Nießen, Susanne Neu, Volker Eckstein, Martin Schiller, Hanns-Martin Lorenz and Lars-Oliver Tykocinski
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Summary:Membrane-coated microvesicles (MVs) have been identified as important mediators in intercellular communication. During the process of apoptosis, dying cells dynamically release MVs. Neutrophils are the most abundant type of leukocytes in the circulation. Due to their very short lifespan, it is likely that they are the source of large amounts of apoptotic cell-derived MVs. Here, we show that MVs released by apoptotic human polymorphonuclear neutrophils (apoPMN-MVs), but not the apoptotic neutrophils themselves, selectively suppress the proliferation of CD25 (IL-2Rα)neg CD127 (IL-7Rα)pos Th cells in a dose-dependent manner. In contrast, the proliferation of total T cells is not affected by MVs. Importantly, apoPMN-MVs suppress the secretion of IL-2 as well as the expression of and signaling via the IL-2 receptor (IL-2R) by CD25negCD127pos Th cells. Addition of IL-7 strongly reduced the suppression of T-cell proliferation by MVs and the addition of IL-2 completely abrogated the suppressive effect. Thus, apoPMN-MVs suppressed a subset of Th cells by downregulating IL-2 and IL-2R expression and signaling. This may represent an important mechanism to prevent the activation and expansion of resting T cells in the absence of sufficient cytokine stimulation, and thereby maintaining immune tolerance.
Item Description:Gesehen am 02.08.2018
Physical Description:Online Resource
ISSN:1521-4141
DOI:10.1002/eji.201546203