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Medizinische Universität Graz

PI, Wadsack

Placental macrophages linking inflammatory pregnancy-related diseases

Macrophages represent the first line of defense in numerous human tissues and are crucial to both acute and resolving immune responses. These remarkably plastic cells are able to adapt to their micro-environment in response to various exo- and endogenous stimuli. Therefore, macrophages have been assigned phenotypes called M1 and M2 (1). However, categorizing macrophages as M1 or M2 is an oversimplified concept, because of their plasticity and adaptability, and a wide range of intermediates has been described (2). Placental Hofbauer cells (HBCs) are tissue macrophages of the feto-placental unit and it is now widely accepted that HBCs are of fetal origin. HBCs are assumed to move through the placental stroma towards sites where they are needed. We and others have shown that HBCs have an M2 anti-inflammatory, regulatory phenotype (CW, AH, GD) (3). HBCs are implicated in placental vasculogenesis and angiogenesis, and we recently demonstrated a regulation of placental endothelial cells by HBC in vitro (GD) (4). Collectively, we hypothesize that HBCs play a major role in maternal immunological tolerance against the fetus by representing a regulatory, tissue-remodeling rather than an inflammatory macrophage phenotype. In this study, the DP-iDP student will address the question if placental inflammation initiated and triggered by maternal metabolic derailments might alter macrophage polarization, thereby contributing to the changes in morphology commonly observed in these placentas. Additionally, macrophage ability to activate feto-placental endothelial cells and their interdependency will be investigated to identify potential functional differences between diverse pregnancy associated inflammatory diseases. We expect that the results from this study will contribute to the knowledge of chronic inflammation in pregnancy and in particular how HBCs of the human placenta impact the pathogenesis of inflammatory pregnancy-related diseases.

 

1. Ornaghi S, Paidas MJ. Upcoming drugs for the treatment of preeclampsia in pregnant women. Expert Rev Clin Pharmacol. 2014;7(5):599-603. doi: 10.1586/17512433.2014.944501.

2. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958–969. doi: 10.1038/nri2448.Exploring

3. Schliefsteiner C, Peinhaupt M, Kopp S, Lögl J, Hiden U, Heinemann A, Desoye G, Wadsack C. Human placental Hofbauer Cells maintain an anti-inflammatory M2 phenotype despite the presence of Gestational Diabetes Mellitus, Frontiers in Immunology, under review.

4. Loegl J, Hiden U, Nussbaumer E, Schliefsteiner C, Cvitic S, Lang I, Wadsack C, Huppertz B, Desoye G. Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis. Reproduction. 2016 Nov;152(5):447-55. doi: 10.1530/REP-16-0159.

 

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