How do pre-pregnancy endometrial macrophages contribute to pregnancy?

Macrophages are professional phagocytes with a wide distribution in all tissues throughout the body. Macrophages play a crucial role in homeostasis and numerous physiological processes beyond innate and adaptive immunity, including cellular debris removal, metabolic regulation, tissue repair, and tissue remodeling. Uterine macrophages are a heterogeneous and highly plastic subset of immune cells regulated by the local microenvironment and, in addition to their anti-inflammatory and anti-infective functions, support the establishment and maintenance of pregnancy. Comprehensive reviews have summarized the role of decidual macrophages during pregnancy. However, the distribution of macrophages in the endometrium prior to pregnancy, their functional remodeling, and the knock-on effects on subsequent pregnancies have not been elucidated. In this review, we focus on 1) how the phenotypes of endometrial macrophages and their interactions with other endometrial cells indicate or contribute to the subsequent pregnancy, 2) the adaptive switching of endometrial macrophages during the initial establishment of pregnancy, 3) and the pregnancy complications and pregnancy-related disorders associated with endometrial macrophages.

Molten salt synthesis of WS2 and MoS2 nanosheets toward efficient gaseous elemental mercury capture.

The development of high-efficient adsorbents for Hg0 capture in a broad temperature window remains a big challenge. Transition-metal dichalcogenides (TMDs) present great prospects owing to their two-dimensional layered structures and abundant active sulfur species. Here, tungsten disulfide (WS2) and molybdenum disulfide (MoS2) nanosheets are easily synthesized via a molten salt route and employed for Hg0 sequestration. With the elevation of the annealing temperature, the Hg0 capture ability of WS2 nanosheet gradually enhances, while MoS2 nanosheet first increases and then decreases. They both display good mercury removal performances in an enlarged temperature range of 60-260 °C. Acidic flue gas components (i.e., SO2 and NO) subtly interfere the mercury removal process, indicating the prospective application potentials of WS2 and MoS2 nanosheets in thermal plants.

Demethylase JMJD2D induces PD-L1 expression to promote colorectal cancer immune escape by enhancing IFNGR1-STAT3-IRF1 signaling.

Programmed death-ligand 1 (PD-L1) is an important immunosuppressive molecule highly expressed on the surface of cancer cells. IFNγ triggered cancer cell immunosuppression against CD8+ T cell surveillance via up-regulation of PD-L1. Histone demethylase JMJD2D promotes colorectal cancer (CRC) progression; however, the role of JMJD2D in cancer immune escape is unknown. Here, we report that both PD-L1 and JMJD2D are frequently overexpressed in human CRC specimens with a significant positive correlation. Genetic ablation of JMJD2D in CRC cells attenuated the expression of PD-L1 and stalled tumor growth in mice, accompanied by the elevated number and effector function of tumor infiltrating CD8+ T cells. Mechanistically, JMJD2D coactivated SP-1 to promote the expression of IFNGR1, which elevated STAT3-IRF1 signaling and promoted PD-L1 expression. Again, JMJD2D is a major coactivator for STAT3-IRF1 axis to enhance PD-L1 transcription in a demethylation activity dependent manner. Furthermore, pharmacological inhibition of JMJD2D conduced to improve the anti-tumor efficacy of PD-L1 antibody as demonstrated by slower tumor growth and higher infiltration and function of CD8+ T cells in the combination of JMJD2D inhibitor 5-c-8HQ and PD-L1 antibody group compared with monotherapy with either agent. These results demonstrate that JMJD2D promotes CRC immune escape by enhancing PD-L1 expression to inhibit the activation and tumor infiltration of CD8+ T cells; targeting JMJD2D has the potential role in promoting the efficacy of anti-PD-1/PD-L1 immunotherapy.

Sacran polysaccharide improves atopic dermatitis through inhibiting Th2 type immune response.

AIMS: This study was aimed to explore whether sacran polysaccharide has a therapeutic effect on atopic dermatitis (AD) and its possible mechanisms. MATERIALS AND METHODS: 2, 4-dinitrochlorobenzene (DNCB)-induced AD mice were treated with 0.2% Sacran, 0.5% Sacran and 0.1% tacrolimus. Through scoring dermatitis severity, measuring ear thickness, cracking behavior, open field test, we evaluated the therapeutic effect of Sacran on DNCB-induced AD mice. CD4+ T cells and CD8+ T cells were evaluated by flow cytometry. The relative expression of Ifng and Il4 were measured by real-time quantitative PCR. KEY FINDINGS: Sacran could relieved the symptoms of DNCB-induced AD mice, such as AD score, ear thickness, and IgE release. Sacran may alleviate dermatitis by inhibiting Th2 activation and reducing IgE release. SIGNIFICANCE: Our research further proved that polysaccharide Sacran has anti-dermatitis effects, and also clarified its mechanism of alleviating dermatitis by inhibiting the activation of Th2 cells and reducing the release of IgE, which provides a theoretical basis for the future clinical transformation of polysaccharide Sacran.

Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell Death.

Follicular helper T (TFH) cells are specialized CD4+ helper T cells that provide help to B cells in humoral immunity. However, the molecular mechanism underlying generation of TFH cells is incompletely understood. Here, we reported that Damage-specific DNA binding protein 1 (Ddb1) was required for expansion of CD4+ helper T cells including TFH and Th1 cells, germinal center response, and antibody response to acute viral infection. Ddb1 deficiency in activated CD4+ T cells resulted in cell cycle arrest at G2-M phase and increased cell death, due to accumulation of DNA damage and hyperactivation of ATM/ATR-Chk1 signaling. Moreover, mice with deletion of both Cul4a and Cul4b in activated CD4+ T cells phenocopied Ddb1-deficient mice, suggesting that E3 ligase-dependent function of Ddb1 was crucial for genome maintenance and helper T-cell generation. Therefore, our results indicate that Ddb1 is an essential positive regulator in the expansion of CD4+ helper T cells.