Monday, 15 September 2014

Placenta-derived exosomes and the immune response to pregnancy

Placental exosomes at the maternal-fetal interface
Reproduced with permission from Mincheva-Nilsson and Baranov Am J Reprod Immunol 2014
(c) 2014 John Wiley & Sons A/S
Exosomes are tiny vesicles (30-100 nm) released from living cells that facilitate intercellular communication (previous post). Exosomes are assembled by and released from the syncytiotrophoblast of human placenta. They carry molecules that could be of critical importance for suppression of the maternal immune response, which might otherwise cause rejection of the fetal allograft.

A brand new review by Lucia Mincheva-Nilsson and Vladimir Baranov (here) summarizes several mechanisms that might be involved and suggest "the placenta is surrounded by a cloud of exosomes that creates a beneficient and protective mileau for its existence." Among these mechanisms (summarized in the Figure) are reduced NK-cell cytotoxicity (through down regulation of the NKG2D receptor), impaired T-cell signalling, apoptosis of activated lymphocytes and effects mediated by TGF-beta that might include recruitment of regulatory T-cells (previous post).

There is more. The syncytiotrophoblast also releases much larger particles (0.2-2 micrometers) often referred to as STBM (for syncytiotrophoblast-derived microparticles). They are not carefully assembled as are exosomes but resemble a form of cellular debris. Importantly, they are pro-inflammatory with the potential to activate the immune system. Mincheva-Nilsson and Baranov hypothesize that placental exosome production may counterbalance the deleterious effects of STBM. They argue that determination of a normal range for the STBM/exosome ratio should be a research priority as it could lead to development of new diagnostic tools.

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