No abstract

The role of natural CD4+CD25+ regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25–mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell–depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell–depleted C3H mice. T reg cell–depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell–depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4+CD25+ T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.

There is overwhelming evidence that mechanical signaling plays a crucial role in development of the ovary, follicle, and oocyte throughout gametogenesis. Emerging data suggest the complexities of mechanotransduction and the biomechanics of oocytes and follicles are integral to understanding of primary ovarian insufficiency, ovarian aging, polycystic ovary syndrome, and applications of fertility preservation.

Research question: What is the psychological impact of the COVID-19 pandemic on infertility patients?Design: An anonymous cross-sectional online survey was sent to patients who attended a large university-affiliated infertility practice in the USA between 1 January 2019 and 1 April 2020. At three different time-points respondents were asked to note their top three stressors, from a list of 10 commonly reported life stressors. Results:The questionnaire was sent to 10,481 patients, with 3604 responses (response rate 34%) received. A total of 2202 non-pregnant female respondents were included in the final analysis. One-third of respondents had a prior diagnosis of an anxiety disorder, and 11% reported taking anxiolytic medications; over one-quarter had a prior diagnosis of a depressive disorder and 11% reported taking antidepressant medications. At all three time-points, infertility was noted to be the most frequent top stressor. Coronavirus was noted to be the third most common stressor among the respondents in early March but, at the time of writing, is similar to that of infertility (63% and 66%, respectively). A total of 6% of patients stated that infertility treatment, including IVF, should not be offered during the COVID-19 pandemic. Conclusion:Despite the unprecedented global pandemic of COVID-19, causing economic and societal uncertainty, the stress of infertility remains significant and is comparable a stressor to the pandemic itself.