SOCS-1 regulates IL-15–driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential

Mice that are deficient in suppressor of cytokine signaling–1 (SOCS-1) succumb to neonatal mortality that is associated with extensive cellular infiltration of many tissues. T cells seem to be necessary for disease, which can be alleviated largely by neutralizing interferon-γ. Examining T cell receptor (TCR) specificity shows that even monospecific T cells can mediate disease in SOCS-1–deficient mice, although disease onset is substantially faster with a polyclonal T cell repertoire. A major phenotype of SOCS-1−/− mice is the accumulation of CD44highCD8+ peripheral T cells. We show that SOCS-1–deficient CD8, but not CD4, T cells proliferate when transferred into normal (T cell–sufficient) mice, and that this is dependent on two signals: interleukin (IL)-15 and self-ligands that are usually only capable of stimulating homeostatic expansion in T cell–deficient mice. Our findings reveal that SOCS-1 normally down-regulates the capacity of IL-15 to drive activation and proliferation of naive CD8 T cells receiving TCR survival signals from self-ligands. We show that such dysregulated proliferation impairs the deletion of a highly autoreactive subset of CD8 T cells, and increases their potential for autoimmunity. Therefore, impaired deletion of highly autoreactive CD8 T cells, together with uncontrolled activation of naive CD8 T cells by homeostatic survival ligands, may provide a basis for the T cell–mediated disease of SOCS-1−/− mice

Blood Pressure Outcomes in NICU-Admitted Infants with Neonatal Hypertension: A Pediatric Nephrology Research Consortium Study

Objective To describe the blood pressure outcomes of infants admitted to the neonatal intensive care unit (NICU) with idiopathic (nonsecondary) hypertension (HTN) who were discharged on antihypertensive therapy. Study design Retrospective, multicenter study of 14 centers within the Pediatric Nephrology Research Consortium. We included all infants with a diagnosis of idiopathic HTN discharged from the NICU on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into (≤6 months, >6 months to 1 year, and >1 year). Comparisons between groups were made with χ2 tests, Fisher's exact tests, and ANOVA. Results Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy >1 year after discharge. Conclusions This multicenter study reports that most infants admitted to the NICU diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN, but should be confirmed prospectively

Strategic Plan: 2018 and Forward - Jefferson Center for Interprofessional Practice & Education

Founded in 2007, the Jefferson Center for Interprofessional Practice and Education (JCIPE) is one of the premier interprofessional education centers in the U.S. Our center is dedicated to improving interprofessional care (IPC) through implementing and evaluating patient-centered education throughout the Thomas Jefferson University curriculum. We offer robust trainings and educational opportunities, provide innovative teaching models and evidence-based practices to help support emerging priorities in healthcare. To coincide with our 10-year anniversary and the transition to new leadership, we engaged the Jefferson Doctor of Management program in Strategic Leadership (DSL) to help us to reimagine and rethink our interests and needs in the increasingly complex and changing environment. With their facilitation we drew on the experience of more than 120 JCIPE stakeholders including co-directors, staff advisors, faculty, deans, student learners, community leaders, health mentors, and patients. We adopted a system-thinking framework and applied interactive design planning methodology to create the design for an ideal center for interprofessional care. From this prototype, we created our new strategic plan, business model, and roadmap. We believe our design experience and deep understanding of IPC will lead us to an even more prominent role as a model of excellence for interprofessional and professional practice and education

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Defining Control Regulation of Dendritic Cell Activation and Immune Homeostasis by SOCS1

AbstractSOCS1 is a key regulator of cytokine signaling and is important for maintaining balance in the immune system. In addition to roles in T, NKT, and macrophage cell function, a new study indicates that SOCS1 modulates dendritic cell activation and may help prevent autoimmunity