Blockage of heme oxygenase-1 abrogates the protective effect of regulatory T cells on murine pregnancy and promotes the maturation of dendritic cells.
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.
Department of Experimental Obstetrics and Gynaecology, Medical Faculty, Otto-von Guericke University of Magdeburg, Magdeburg, Germany.
Anne
A
Schumacher
Paul Ojiambo
PO
Wafula
Ana
A
Teles
Tarek
T
El-Mousleh
Nadja
N
Linzke
Maria Laura
ML
Zenclussen
Stefanie
S
Langwisch
Kristina
K
Heinze
Ivonne
I
Wollenberg
Pablo Ariel
PA
Casalis
Hans-Dieter
HD
Volk
Stefan
S
Fest
Ana Claudia
AC
Zenclussen
D000022:Abortion, Spontaneous / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005313:Fetal Death / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000235:genetics; D011524:Protoporphyrins / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; D004791:Enzyme Inhibitors; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018836:Inflammation Mediators; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D051547:Heme Oxygenase-1