Transfer of regulatory T cells into abortion-prone mice promotes the expansion of uterine mast cells and normalizes early pregnancy angiogenesis.
Implantation of the fertilized egg depends on the coordinated interplay of cells and molecules that prepare the uterus for this important event. In particular, regulatory T cells (Tregs) are key regulators as their ablation hinders implantation by rendering the uterus hostile for the embryo. In addition, the adoptive transfer of Tregs can avoid early abortion in mouse models. However, it is still not defined which mechanisms underlie Treg function during this early period. Cells of the innate immune system have been reported to support implantation, in part by promoting angiogenesis. In particular, uterine mast cells (uMCs) emerge as novel players at the fetal-maternal interface. Here, we studied whether the positive action of Tregs is based on the expansion of uMCs and the promotion of angiogenesis. We observed that abortion-prone mice have insufficient numbers of uMCs that could be corrected by the adoptive transfer of Tregs. This in turn positively influenced the remodeling of spiral arteries and placenta development as well as the levels of soluble fms-like tyrosine kinase 1 (sFlt-1). Our data suggest an interplay between Tregs and uMCs that is relevant for the changes required at the feto-maternal interface for the normal development of pregnancy.
Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
Katja
K
Woidacki
Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
Nicole
N
Meyer
Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
Anne
A
Schumacher
Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
Alexandra
A
Goldschmidt
Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Germany.
Marcus
M
Maurer
Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
Ana Claudia
AC
Zenclussen
D000022:Abortion, Spontaneous / Q000276:immunology / Q000378:metabolism; D019264:Adoptive Transfer; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D005313:Fetal Death; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000276:immunology*; D010920:Placenta / Q000098:blood supply / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014599:Uterus / Q000098:blood supply* / Q000276:immunology*
C526204:Fitm1 protein, mouse; D008565:Membrane Proteins; D000804:Angiotensin II