Platelet-Derived Ectosomes Reduce NK Cell Function

doi:10.4049/jimmunol.1502658

2016-09-01

Salima Sadallah *

Laurent Schmied

Ceylan Eken

Hojjatollah Nozad Charoudeh

Francesca Amicarella

Jürg A. Schifferli

DOI：10.4049/jimmunol.1502658

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En 中文

Platelet (PLT) transfusions are potentially life saving for individuals with low PLT numbers; however, previous work revealed that PLT transfusions are associated with increased infection risk. During storage, PLT intended for transfusion continuously shed ectosomes (Ecto) from their surface, which express immunomodulatory molecules like phosphatidylserine or TGF-beta 1. Recently, PLT-Ecto were shown to reduce proinflammatory cytokine release by macrophages and to favor the differentiation of naive T cells toward regulatory T cells. Whether PLT-Ecto modify NK cells remains unclear. We exposed purified NK cells and full PBMCs from healthy donors to PLT-Ecto. We found a reduced expression of several activating surface receptors (NKG2D, NKp30, and DNAM-1) and decreased NK cell function, as measured by CD107a expression and IFN-gamma production. Pretreatment of PLT-Ecto with anti-TGF-beta 1 neutralizing Ab restored surface receptor expression and NK cell function. We further observed a TGF-beta 1 mediated upregulation of miR-183, which, in turn, reduced DAP12, an important protein for stabilization and downstream signaling of several activating NK cell receptors. Again, these effects could antagonized, in part, when PLT-Ecto were pre-incubated with anti-TGF-beta 1 Ab. Erythrocyte Ecto did not affect NK cells. Polymorphonuclear cell Ecto expressed MHC class I and inhibited NK cell function. In addition, they induced the secretion of TGF-beta 1 by NK cells, which participated in an auto/paracrine manner in the suppressive activity of polymorphonuclear cell-derived Ecto. In sum, our study showed that PLT-Ecto could inhibit NK cell effector function in a TGF-beta 1-dependent manner, suggesting that recipients of PLT transfusions may experience reduced NK cell function.

Keyword:

ALLOGENEIC BLOOD-TRANSFUSION

NATURAL-KILLER-CELLS

MICROPARTICLES

HLA

NEUTROPHILS

EXPRESSION

TRIGGERS

STORAGE

ACTIVATION

RECEPTORS