FOXP3 exon 2 controls Treg stability and autoimmunity.

Differing from the mouse Foxp3 gene that encodes only one protein product, human FOXP3 encodes two major isoforms through alternative splicing-a longer isoform (FOXP3 FL) containing all the coding exons and a shorter isoform lacking the amino acids encoded by exon 2 (FOXP3 ΔE2). The two isoforms are naturally expressed in humans, yet their differences in controlling regulatory T cell phenotype and functionality remain unclear. In this study, we show that patients expressing only the shorter isoform fail to maintain self-tolerance and develop immunodeficiency, polyendocrinopathy, and enteropathy X-linked (IPEX) syndrome. Mice with Foxp3 exon 2 deletion have excessive follicular helper T (TFH) and germinal center B (GC B) cell responses, and develop systemic autoimmune disease with anti-dsDNA and antinuclear autoantibody production, as well as immune complex glomerulonephritis. Despite having normal suppressive function in in vitro assays, regulatory T cells expressing FOXP3 ΔE2 are unstable and sufficient to induce autoimmunity when transferred into Tcrb-deficient mice. Mechanistically, the FOXP3 ΔE2 isoform allows increased expression of selected cytokines, but decreased expression of a set of positive regulators of Foxp3 without altered binding to these gene loci. These findings uncover indispensable functions of the FOXP3 exon 2 region, highlighting a role in regulating a transcriptional program that maintains Treg stability and immune homeostasis.

Asthenopia Among University Students: The Eye of the Digital Generation.

BACKGROUND: Asthenopia or eye strain is one of the major medical problems that students face during their academic years. OBJECTIVES: The aim of this study is to determine the prevalence of asthenopia among a sample of university students attending various majors and to identify the risk factors for its development. METHODS: This is a cross sectional study conducted on students attending various faculties at the American University of Beirut during the spring semester of 2019. Students were asked to fill a self-administered anonymous questionnaire that inquired about demographics, use of digital devices, symptoms of asthenopia, possible risk factors and protective measures. A bivariate analysis was performed to correlate asthenopia with the different variables. A multivariate analysis was then conducted to determine the extent of contribution of the different variables to asthenopia after controlling for confounding variables. RESULTS: The prevalence of asthenopia was found to be 67.8% with blurred vision being the most reported symptom (27.0%). A bivariate analysis was used to assess the association between asthenopia and the following variables: demographics, digital device use, reasons for using digital devices, and preventive methods. Age, being a continuous variable, was analyzed using an independent t- test. For the variables that were found to be have a p-value < 0.2, a multiple logistic regression was performed. Old age was found to be a protective factor for asthenopia, with 0.693 times reduction in asthenopia for every increase in year of age. Using the device for communication for less than four hours (p=0.012), using the device for less than four hours per day (p=0.000) and pattern of using the device for less than three years (p=0.023) were significant in being negatively associated with asthenopia. As for preventative measures that protect users from digital eyestrain, we found that using eye drops (p=0.004; OR=0.375) and taking regular breaks (p=0.000; OR= 0.399) were protective factors whereas using adjustable screens was a risk factor (p=0.000; OR=3.083). CONCLUSION: Asthenopia was found to be of non-negligible prevalence among this sample of university students. The results of this study highlight the importance of establishing awareness campaigns and encourage the introduction of targeted screenings for asthenopia among college students.