Dataset Information

Frontline Science: Myeloid-derived suppressor cells (MDSCs) facilitate maternal-fetal tolerance in mice.

ABSTRACT: During successful pregnancy, a woman is immunologically tolerant of her genetically and antigenically disparate fetus, a state known as maternal-fetal tolerance. How this state is maintained has puzzled investigators for more than half a century. Diverse, immune and nonimmune mechanisms have been proposed; however, these mechanisms appear to be unrelated and to act independently. A population of immune suppressive cells called myeloid-derived suppressor cells (MDSCs) accumulates in pregnant mice and women. Given the profound immune suppressive function of MDSCs, it has been suggested that this cell population may facilitate successful pregnancy by contributing to maternal-fetal tolerance. We now report that myeloid cells with the characteristics of MDSCs not only accumulate in the circulation and uterus of female mice following mating but also suppress T cell activation and function in pregnant mice. Depletion of cells with the phenotype and function of MDSCs from gestation d 0.5 through d 7.5 resulted in implantation failure, increased T cell activation, and increased T cell infiltration into the uterus, whereas induction of MDSCs restored successful pregnancy and reduced T cell activation. MDSC-mediated suppression during pregnancy was accompanied by the down-regulation of L-selectin on naïve T cells and a reduced ability of naïve T cells to enter lymph nodes and become activated. Because MDSCs regulate many of the immune and nonimmune mechanisms previously attributed to maternal-fetal tolerance, MDSCs may be a unifying mechanism promoting maternal-fetal tolerance, and their induction may facilitate successful pregnancy in women who spontaneously abort or miscarry because of dysfunctional maternal-fetal tolerance.

SUBMITTER: Ostrand-Rosenberg S

PROVIDER: S-EPMC5380379 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background: Stroke patients are at risk of acquiring secondary infections due to stroke-induced immune suppression (SIIS). Immunosuppressive cells comprise myeloid-derived suppressor cells (MDSCs) and immunosuppressive interleukin 10 (IL-10)-producing monocytes. MDSCs represent a small but heterogeneous population of monocytic, polymorphonuclear (or granulocytic), and early progenitor cells ("early" MDSC), which can expand extensively in pathophysiological conditions. MDSCs have been shown to exert strong immune-suppressive effects. The role of IL-10-producing immunosuppressive monocytes after stroke has not been investigated, but monocytes are impaired in oxidative burst and downregulate human leukocyte antigen-DR isotype (HLA-DR) on the cell surface. Objectives: The objective of this work was to investigate the regulation and function of MDSCs as well as the immunosuppressive IL-10-producing monocytes in experimental and human stroke. Methods: This longitudinal, monocentric, non-interventional prospective explorative study used multicolor flow cytometry to identify MDSC subpopulations and IL-10 expression in monocytes in the peripheral blood of 19 healthy controls and 27 patients on days 1, 3, and 5 post-stroke. Quantification of intracellular STAT3p and Arginase-1 by geometric mean fluorescence intensity was used to assess the functionality of MDSCs. In experimental stroke induced by electrocoagulation in middle-aged mice, monocytic (CD11b+Ly6G-Ly6Chigh) and polymorphonuclear (CD11b+Ly6G+Ly6Clow) MDSCs in the spleen were analyzed by flow cytometry. Results: Compared to the controls, stroke patients showed a relative increase in monocytic MDSCs (percentage of CD11b+ cells) in whole blood without evidence for an altered function. The other MDSC subgroups did not differ from the control. Also, in experimental stroke, monocytic, and in addition, polymorphonuclear MDSCs were increased. The numbers of IL-10-positive monocytes did not differ between the patients and controls. However, we provide a new insight into monocytic function post-stroke since we can report that a differential regulation of HLA-DR and PD-L1 was found depending on the IL-10 production of monocytes. IL-10-positive monocytes are more activated post-stroke, as indicated by their increased HLA-DR expression. Conclusions: MDSC and IL-10+ monocytes can induce immunosuppression within days after stroke.

Dataset Information

Frontline Science: Myeloid-derived suppressor cells (MDSCs) facilitate maternal-fetal tolerance in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets