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.
One of the leading factors in breast cancer-related death, is tumor recurrence despite apparently successful therapeutic intervention. Recurrent disease is linked to the presence of a minimal population of residual cancer cells that are hard to detect; therefore, little is known about these cells. In this episode, Martin Jechlinger and colleagues present several lines of evidence to show that residual cells have a distinct transcriptional profile that results in changes in metabolism and elevated ROS production. Together, these results provide a better understanding of these cells and suggest potential targeting strategies.
Invariant natural killer T (iNKT) cells are a prominent component of the liver-resident immune cell population. These cells are involved in both liver regeneration and regulation of the local immune response; however, little is known about how iNKT cells are maintained within the liver. In this episode, Xian Li reveals that stimulation of cell surface receptor OX40 induces a pyroptotic cell death in liver iNKT cells that exacerbates liver injury and inflammation. The results of this study support the OX40 pathway as a potential therapeutic target for limiting liver damage.
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.