Research Repository

PreImplantation factor (PIF*) regulates systemic immunity and targets protective regulatory and cytoskeleton proteins

Barnea, Eytan R and Hayrabedyan, Soren and Todorova, Krassimira and Almogi-Hazan, Osnat and Or, Reuven and Guingab, Joy and McElhinney, James and Fernandez, Nelson and Barder, Timothy (2016) 'PreImplantation factor (PIF*) regulates systemic immunity and targets protective regulatory and cytoskeleton proteins.' Immunobiology, 221 (7). pp. 778-793. ISSN 0171-2985

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Secreted by viable embryos, PIF is expressed by the placenta and found in maternal circulation. It promotes implantation and trophoblast invasion, achieving systemic immune homeostasis. Synthetic PIF successfully transposes endogenous PIF features to non-pregnant immune and transplant models. PIF affects innate and activated PBMC cytokines and genes expression. We report that PIF targets similar proteins in CD14+, CD4+ and CD8+ cells instigating integrated immune regulation. PIF-affinity chromatography followed by mass-spectrometry, pathway and heatmap analysis reveals that SET-apoptosis inhibitor, vimentin, myosin-9 and calmodulin are pivotal for immune regulation. PIF acts on macrophages down-stream of LPS (lipopolysaccharide-bacterial antigen) CD14/TLR4/MD2 complex, targeting myosin-9, thymosin-α1 and 14-3-3eta. PIF mainly targets platelet aggregation in CD4+, and skeletal proteins in CD8+ cells. Pathway analysis demonstrates that PIF targets and regulates SET, tubulin, actin-b, and S100 genes expression. PIF targets systemic immunity and has a short circulating half-life. Collectively, PIF targets identified; protective, immune regulatory and cytoskeleton proteins reveal mechanisms involved in the observed efficacy against immune disorders.

Item Type: Article
Uncontrolled Keywords: PreImplantation factor (PIF); Immune targets; Oxidative stress; Protein misfolding; Immune regulation; Inflammation control; Embryo tolerance
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 14 Mar 2016 12:42
Last Modified: 15 Jan 2022 00:23

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