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Regulation of MR1 expression and function in airway inflammation
No full textMucosal-associated invariant T (MAIT) cells are an innate-like T cell subset important in the early response to bacterial and viral lung pathogens. Upon activation, MAIT cells are capable of immediate effector function, releasing cytotoxic molecules and pro-inflammatory cytokines in mucosal tissue. MAIT cells are restricted by the MHC class I-related molecule MR1, which presents non-protein antigens such as small molecule metabolites generated as byproducts of microbial riboflavin biosynthesis. At rest, MR1 proteins primarily reside in the ER or endosomal compartments. Ligand-bound MR1 translocates to the cell surface through distinct trafficking mechanisms for presentation of antigens from intracellular and extracellular pathogens. The abundance of both MAIT cells and putative antigen sources in the mucosal periphery necessitates strict control of MR1 antigen presentation to avoid inappropriate MAIT cell activation. These studies characterize novel regulatory mechanisms of MR1 transcriptional expression, endosomal trafficking, and recycling pathways. Dysregulation of these pathways in the context of environmental toxins like cigarette smoke (CS) and inflammatory diseases like chronic obstructive pulmonary disease (COPD) leads to altered MR1 expression, dysfunctional MAIT cell activation, and pathogenic feed-forward inflammatory signaling cycles. Together, this work demonstrates that regulation of MR1 transcription and antigen presentation is critical to balance appropriate and proportional MAIT cell responses to respiratory insults
OHSU Fact Book, 2011
No full textOregon Health & Science University is the state's only comprehensive public academic health center. This publication was prepared by the OHSU Office of the Registrar using a variety of data sources maintained by other offices in the University. The purpose of this document is to provide data about academic programs, students, faculty and staff, and other basic information in a user-friendly format for the OHSU community and public
The effects of topographical micropatterning on acute thrombosis and endothelial cell (patho)physiology
No full textCardiovascular disease affects nearly half of all U.S. adults and is the leading cause of death worldwide. Advanced cases are often treated through vascular grafting to bypass occluded vessels. Synthetic vascular graft materials suffer from patency complications due to thrombosis and neointimal growth impeding the materials’ long-term function for small-diameter applications. Thus, there is a critical unmet need for improved biocompatible small-diameter vascular grafts to support long-term patient outcomes and reduce re-intervention procedures. The in vitro establishment of an endothelial layer on synthetic vascular grafts has been suggested to be a solution due to the endothelial cells’ (ECs) homeostatic capabilities to prevent thrombus formation and limit immunogenicity. Therefore, vascular graft material surfaces which limit thrombosis and support EC growth and function are a significant clinical need. A surface modification that has the potential to attenuate thrombosis while promoting an endothelium is topographical micropatterning on luminal biomaterial surfaces. Topographical micropatterning is a physical modification that downregulates platelet adhesion and activation in static culture while promoting endothelial migration and function. This work provides a systematic study of the in vitro thrombogenicity of micropatterned hydrogel surfaces with varying feature sizes as well as ex vivo assessments of acute thrombogenesis on the modified grafts. Additionally, this work utilizes topographical micropatterns as a platform to induce endothelial elongation and cytoskeletal alignment to investigate changes in mechanotransduction pathways independent of blood fluid shear stress. The culmination of these findings aids in the design of novel small-diameter synthetic vascular grafts and provide insight into the mechanisms by which elongated ECs transduce an anti-inflammatory phenotype
Two and a half apples a day keeps the PA away: increasing fruit and vegetable consumption while decreasing added sugar in adolescents
Get PDFAmerican’s are eating too little fruits and vegetables and too much added processed sugar. Meanwhile, three out of five Americans eat more than the daily recommended amount of processed added sugar in any given day. Eating fruits and vegetables is associated with decreased overall mortality
