In this video collection, authors of findings published in The Journal of Clinical Investigation present personally guided tours of their results. The JCI accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
Mice with defects in the stem cell factor receptor Kit lack mast cells, which have been implicated in a variety of inflammatory diseases such as arthritis. There are strain-specific differences in how mast cell-deficient animals manifest model diseases, leading to questions about the role of mast cells in certain pathologies. In this episode, Peter Nigrovic and colleagues investigate differences in mast cell-deficient mice that lead to differential susceptibility to IgG-induced arthritis. Using a series of bone marrow and cell transplantation experiments, Nigrovic and coworkers reveal that marrow and stromal context determine the role of mast cells in inflammation and that megakaryocytes can directly mediate inflammation.
Individuals with mutations in the gene encoding the CD11b are at high risk of developing the autoimmune disease systemic lupus erythematosus (SLE). In this episode, Mariana Kaplan and Vineet Gupta reveal that SLE-associated mutation in the CD11b-encoding gene that result in reduced CD11b function results in elevated levels of type I IFN. Moreover, in mouse SLE models, treatment with a molecule that activates CD11b reduced type I signaling and reduced end-organ damage. Together, the results of this study support further exploration of CD11b activation as a therapeutic strategy for SLE.
Atherosclerosis can result in severe outcomes, including heart attack and stroke. The presence of atherosclerotic plaques is one of the first signs of disease; however, there is currently no accurate way to predict which patients are at the highest risk of adverse cardiovascular events. In this episode, Manuel Mayr and colleagues use a proteomic approach to compare extracellular matrix proteins in lesions from asymptomatic and symptomatic patients. Their work identifies a 4-biomarker signature that has potential to improve risk prediction and management of heart disease.
Immune-mediated rejection of donor tissues is one of the largest challenges in transplant biology. While routine biopsy to monitor transplanted organs can be informative, this procedure is invasive and carries several risks. In this episode, Prashanth Vallabhajosyula and colleagues evaluated changes in transplant-derived exosomes in murine models and human transplant recipients. Their work indicates that changes in donor-derived exosomes can be used to noninvasively monitor transplant rejection.
Obesity, diabetes, and other metabolic diseases have known underlying genetic causes; however, environmental factors also play an important role in the onset and development of metabolic dysfunction. In this episode, Mitchell Lazar and Raymond Soccio discuss their study, which compared high fat-diet-induced effects on gene expression and the epigenome in mice genetically prone to diet-induced obesity and in animals that are resistant to diet-induced metabolic disease. They find that the thermogenic gene Ucp1 is repressed in the obesity-prone mice, but that either cold-exposure or treatment with the insulin-sensitizing drug rosiglitazone restores Ucp1 expression to levels similar to that in obesity-resistant strains. The results of this study demonstrate that genetic defects in metabolism can be rescued by environmentally-driven epigenomic modifications.