A deeper understanding of the immunological events during pregnancy will provide novel insights into the pathogenesis of pregnancy complications. The fundamental function of T follicular helper (Tfh) cells is to provide cognate help to B cells. Dysregulations of Tfh-cell function and/or development can result in various immunological diseases. However, the role and characteristics of Tfh cells during pregnancy remain unknown. Herein, an allogeneic-normal-pregnant mouse model was used, and we found that the CD4+ T cells residing at the uterus and placenta (UP) displayed a Tfh-like phenotype; and the UP-derived CD4+CXCR5hiPD-1hi and CD4+CXCR5hiICOShi Tfh cells, which showed a memory/activation phenotype, reached their peak at mid-pregnancy. These Tfh cells were located abundantly in the uterus at mid-pregnancy, but greatly increased in the placenta at late-pregnancy. Furthermore, increased foetal resorption by PDL1 blockade correlated with enhanced accumulation of Tfh cells and upregulated expressions of ICOS and PD-1 on these cells. Collectively, our findings are the first to indicate that an adequate and balanced accumulation of Tfh cells during gestation is likely to help maintaining a successful pregnancy, whereas an excessively high level of these cells could lead to abortion.
Problem: Maternal immune system tolerance to the semiallogeneic fetus is critical for a successful pregnancy. Studies have shown that myeloid-derived suppressor cells (MDSCs) play an important role in maintaining feto-maternal tolerance. However, the mechanisms remain poorly understood. Methods: Flow cytometry was used to evaluate the percentage of MDSCs in an allogeneic-normal-pregnant mouse model during different periods of gestation. We further assessed the percentage of MDSCs and their subtypes (granulocytic MDSCs [GR-MDSCs] and monocytic MDSCs [MO-MDSCs]) in a spontaneous abortion mouse model. The levels of the immunosuppressive molecules ARG-1, iNOS, IL-10, and TGF-β in MDSCs were also evaluated. MDSCs were depleted by anti-Gr-1 injection, and the resorption rate was calculated. The cytotoxicity of decidual natural killer (NK) cells was evaluated, and the percentage of regulatory NK (NKreg) cells and regulatory T lymphocytes (Tregs) were evaluated. Results: Myeloid-derived suppressor cells was accumulated in a time-dependent manner during pregnancy. However, the percentage of MDSCs was decreased in the spontaneous abortion mice compared with that in the control mice. In addition, the levels of ARG-1, iNOS, IL-10, and TGF-β in MDSCs decreased differentially. Finally, depletion of MDSCs was associated with increased rates of resorption and the proportion of NKreg and Treg cells in uterine tissues; meanwhile, the cytotoxicity of decidual NK cells was upregulated by increasing the level of perforin, granzyme B, and natural killer group protein 2 D-activating NK receptor (NKG2D). Conclusion: Depletion of MDSCs may cause pregnancy loss, while upregulating the cytotoxicity of decidual NK cells and increasing NKreg and Treg cell numbers. K E Y W O R D S cytotoxicity, decidual natural killer cells, myeloid-derived suppressor cells, pregnancy loss, regulatory NK cells, regulatory T lymphocytes How to cite this article: Ren J, Zeng W, Tian F, et al. Myeloidderived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells. Am
Asteraceae are distinguishable by their head‐like inflorescence called a capitulum. There are a variety of capitulum types due to different combinations of different composing florets. Morphological evolution of capitula must involve homoplasy under selective constraints. Therefore, a comparative examination of ontogenies of divergent capitula among phylogenetically close taxa is important to investigate the genetic and molecular bases of this trait. In the subtribe Artemisiinae, tribe Anthemideae, three closely related genera have different flower heads: Chrysanthemum with the radiate, Ajania with the disciform, and Stilpnolepis with the discoid capitula. Through observations using scanning electron microscopy, we examined the morphogenetic processes of flower heads of representative species of these genera. The morphological differentiation of the discoid from the radiate/disciform capitula occurred early in the floral initiation stage. The development of the ray/marginal florets of the radiate/disciform capitula lagged behind the outermost disc florets throughout the phases of floral initiation and floral organogenesis. Primordia of their 1–2 dorsal corolla lobes and all stamens ceased to grow soon after initiation. In contrast, all florets on a discoid capitulum developed equally in rates and modes into bisexual actinomorphic flowers. Differentiation between the radiate and the disciform capitula occurred late during the floral maturation stage. Our data provided evidence to the interpretation that uniformly acropetal development only occurs in species with homogamous flower heads, and to the idea that the timing of ontogenetic divergence between taxa is positively correlated with the phylogenetic distance of the taxa.
XCL1-XCR1 chemokine pathway promotes trophoblast invasion by increasing matrix metalloproteinase activity in human first-trimester placenta.
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