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Immunology - Obstetrics - Women's Health

Blockage of Heme Oxygenase-1 Abrogates the Protective Effect of Regulatory T Cells on Murine Pregnancy and Promotes the Maturation of Dendritic Cells
Published: Friday, August 10, 2012
Author: Anne Schumacher et al.

by Anne Schumacher, Paul Ojiambo Wafula, Ana Teles, Tarek El-Mousleh, Nadja Linzke, Maria Laura Zenclussen, Stefanie Langwisch, Kristina Heinze, Ivonne Wollenberg, Pablo Ariel Casalis, Hans-Dieter Volk, Stefan Fest, Ana Claudia Zenclussen

Regulatory T cells (Treg) play an important role in fetal protection. They expand during normal pregnancy and protect fetal antigens from maternal effector cells. Their effect is associated with the up-regulation of tolerance-associated molecules at the fetal-maternal interface. Among these, Heme Oxygenase-1 (HO-1, coded by Hmox1) is of special importance as its blockage correlates with increased abortion rates and its up-regulation positively affects pregnancy outcome. Here, we aimed to investigate whether the protective effect of Treg is mediated by HO-1 in a mouse model. HO-1 blockage by Zinc Protoporhyrin (ZnPPIX) abrogated the protective effect of Treg transfer. We found that HO-1 is important in maintaining maternal dendritic cells (DCs) in an immature state, which contributes to the expansion of the peripheral Treg population. This brings to light one essential pathway through which Treg mediates the semi-allogeneic fetus tolerance.