The mechanisms behind the survival of the fetus during gestation are being actively investigated. Some of current theories as to how the maternal immune system actively tolerates the fetus include fetal tissue 
depletion of tryptophan, an essential amino acid necessary for rapidly dividing cells thereby hindering T cell proliferation, expression of human leukocyte antigen G which blocks the activation of natural killer cells, a shift to a Th2 cytokine profile and apoptosis of maternal activated lymphocytes due to the trophoblastic expression of Fas ligand. Recently, a special subset of T cells, regulatory T cells has been revelead as important for the survival, acceptance and immune tolerance of developing fetuses. Successful human and murine pregnancies are clearly associated with an increase in Treg frequency whereas diminished number and function of these cells results in abortion in mice and is associated with miscarriage in humans. HO-1, a microsomal enzyme involved in the rate-limiting step in the degradation of heme to biliverdin, has been found to be protective in many disease models through its anti-inflammatory, anti-apoptotic and anti-proliferative actions. This enzyme allows acceptance of mouse allograft while its down-regulation results in acute rejection. Furthermore, successful xenograft transplantation is attributed to activation of non-inflammatory protective genes including HO-1. Absence of HO-1 expression/activity leads to intrauterine fetal death and mating of heterozygote Hmox1 mice leads to around 6% knockout progeny instead of the expected 25% as for Mendelian rules. We have shown that HO-1 up-regulation by Cobalt Protoporphyrin IX as well as by gene therapy results in fetal protection. Novel data links HO-1 and Treg pathways as induction of HO-1 in combination with Donor Specific Transfusion resulted in successful cardiac transplantation by boosting CD4 + CD25 + T cells. The aim of the present study was to analyze whether the protective effect of Treg in the CBA/J6DBA/2J abortion model is Tulathromycin B mediated by HO-1. Our data indicate that HO-1 blockage abrogates the protective effect of Treg and provokes abortion. Moreover, blocking HO-1 in Treg donors prevented the ability of these cells to rescue from abortion. We were also able to show that HO-1 blockage renders dendritic cells to a mature state that in turn promotes the action of effector T cells. Accordingly, in vivo HO-1 augmentation by CoPPIX keeps DCs in an immature state. This facilitates the expansion and action of Treg. All together, our data demonstrated the importance of the interplay between HO-1 and Treg for maternal tolerance Butenafine hydrochloride towards the allogeneic fetus. Pregnancy establishment and maintenance constitutes a huge challenge for the maternal immune system as it has to on the one hand be able to combat infections and on the other hand tolerate the fetus expressing foreign paternal antigens. It has been shown that regulatory T cells are of importance in achieving tolerance and avoiding maternal effector cells to attack fetal structures. In the present study, we aimed to investigate whether the proven protective effect of regulatory T cells on pregnancy outcome is mediated by the enzyme Heme oxygenase-1 as their interplay has been already described for other pathologies. It is known that HO-1 has profound effects on reproductive steps. It affects ovulation and fertilization in mice and also known to be highly expressed by trophoblast cells already at early pregnancy stages. HO-1 diminution is related to murine and human pregnancy complications while its augmentation can rescue from fetal death. It is known that some of the protective effects of HO-1 in pregnancy are mediated by carbon monoxide. Furthermore, HO-1 micro-polymorphism in women is related to repeated miscarriage.