Natural killer (NK) cells accumulate at the maternal-fetal interface in large numbers, but their exact roles in successful pregnancy remain poorly defined. Here, we provide evidence that T H 17 cells and local inflammation can occur at the maternal-fetal interface during natural allogenic pregnancies. We found that decidual NK cells promote immune tolerance and successful pregnancy by dampening inflammatory T H 17 cells via IFN-γ secreted by the CD56 bright CD27 + NK subset. This NK-cell-mediated regulatory response is lost in patients who experience recurrent spontaneous abortions, which results in a prominent T H 17 response and extensive local inflammation. This local inflammatory response further affects the regulatory function of NK cells, leading to the eventual loss of maternal-fetal tolerance. Thus, our data identify NK cells as key regulatory cells at the maternal-fetal interface by suppressing T H 17-mediated local inflammation.regulatory NK cells | fetomaternal tolerance D uring pregnancy, allogeneic fetal cells invade the maternal decidua but they are protected from the maternal immune system. This invasion of extraembryonic trophoblasts does not harm gestation during normal pregnancy; it establishes tolerance at the maternal-fetal interface (1), (2), although the mechanism of such tolerance is not clear. In addition, inflammatory responses induced by a variety of mechanisms can result in embryo loss, but mild inflammation can be effectively controlled through regulatory mechanisms to maintain successful pregnancy (3). Thus, suppression of strong inflammatory responses is essential to ensure normal pregnancy (4, 5), although the mechanisms involved in regulating local inflammation without compromising overall maternal immunity during a successful pregnancy remain unknown.Multiple mechanisms are potentially involved in promoting immune tolerance during pregnancy. For example, T H 2 cytokine polarization (6-9), the expression of the Fas ligand on trophoblast cells (10), and the inhibition of complement activation (11) are crucial for ensuring tolerance at the maternal-fetal interface. In addition, a delicate balance exists between inhibitory (PD-L1, Stat3, and TGF-β1) and stimulatory (CD80 and CD86) signals during the establishment of immune privilege (12-18). Furthermore, studies have shown that galectin-1 (19) and indoleamine 2,3-dioxygenase (20) play pivotal roles in maternal-fetal tolerance. Several types of immune cells, such as CD4 + CD25 + regulatory T cells, are also essential in the generation of maternal-fetal tolerance in mice and humans (7,(21)(22)(23)(24). Furthermore, natural killer (NK) T cells and immature dendritic cells have been reported to promote the expansion of Treg cells that confer protection of the fetus (19).Despite considerable progress, many questions remain unanswered. The most striking feature at the maternal-fetal interface is the accumulation of NK cells, which account for ∼60-90% of immune cells in the decidua in humans during early pregnancy (25)(26)(27)(28)(29) and a...

Background: Medical students experience depression and anxiety at a higher rate than the general population or students from other specialties. While there is a growing literature on the high prevalence of depression and anxiety symptoms and about potential risk factors to the prevalence of depression and anxiety symptoms among medical students, there is a paucity of evidence focused on the prevalence of depression and anxiety symptoms and associations with family function, social support and coping styles in Chinese vocational medicine students. This study aims to investigate the prevalence of depression and anxiety symptoms among Chinese medical students and assess the correlation between depression/anxiety symptoms and family function, social support and coping styles. Methods: A sample of 2057 medical students from Chongqing Medical and Pharmaceutical College in China was investigated with a self-report questionnaire, which included demographic information, Zung self-rating depression scale, Zung Self-Rating Anxiety Scale, Family APGAR Index, Social Support Rating Scale and Trait Coping Style Questionnaire. Results: The prevalence of depression and anxiety symptoms among the medical students was 57.5 and 30.8%, respectively. Older students(≥20 years) experienced higher levels of depression and anxiety. More depression and anxiety symptoms were exhibited among students with big financial burden, big study-induced stress and poor sleep quality. Students with large employment pressure showed more anxiety symptoms. Students who live alone or had bad relationship with their lovers or classmates or friends showed higher depression and anxiety scores. Depression and anxiety symptoms had highly significant correlations with family functioning, social support and coping style. Conclusions: Academic staffs should take measures to reduce depression and anxiety among medical students and to provide educational counseling and psychological support for students to cope with these problems.

Summary The identification of developmental stages in natural killer (NK) cells, especially in human NK cells, has lagged for decades. We characterize four novel populations defined by CD11b and CD27, which can represent the distinct stages of human NK cells from different tissues. Nearly all NK cells from peripheral blood are CD11b+ CD27− populations whereas NK cells from cord blood have CD11b+ CD27− and CD11b+ CD27+ populations. Interestingly, we have found large CD11b− CD27− populations of NK cells from deciduas. We also demonstrate that each population could be characterized by unique functional and phenotypic attributes. CD11b− CD27− NK cells display an immature phenotype and potential for differentiation. CD11b− CD27+ and CD11b+ CD27+ NK cells show the best ability to secrete cytokines. CD11b+ CD27− NK cells exhibit high cytolytic function. We demonstrate that human NK cells at different developmental stages have special functions and describe a new model of human NK cell differentiation.

Cervical cancer is the most common malignant disease responsible for the deaths of a large number of women in the developing world. Although certain strains of human papillomavirus (HPV) have been identified as the cause of this disease, events that lead to formation of malignant tumors are not fully clear. STAT3 is a major oncogenic transcription factor involved in the development and progression of a number of human tumors. However, the mechanisms that result in loss of control over STAT3 activity are not understood. Gene associated with Retinoid-Interferon-induced Mortality-19 (GRIM-19) is a tumor-suppressive protein identified using a genetic technique in the interferon/retinoid-induced cell death pathway. Here, we show that reduction in GRIM-19 protein levels occur in a number of primary human cervical cancers. Consequently, these tumors tend to express a high basal level of STAT3 and its downstream target genes. More importantly, using a surrogate model, we show that restoration of GRIM-19 levels reestablishes the control over STAT3-dependent gene expression and tumor growth in vivo. GRIM-19 suppressed the expression of tumor invasion- and angiogenesis-associated factors to limit tumor growth. This study identifies another major novel molecular pathway inactivated during the development of human cervical cancer.