This series showcases video summaries of new findings published in the Journal of Clinical Investigation. This format allows authors to to provide a personally guided tour of their results and makes the research more accessible to a broad readership. The JCI accepts videos from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
Injury to the central nervous system (CNS) results in a cascade of events that leads to cell death and neurodegeneration. Recent studies have shown that T cells infiltrate sites of neuronal injury and are protective against damage, though it is not clear how these cells are activated or mediate neuroprotective effects. In this episode, Jonathan Kipnis, James Walsh, and Frauke Zipp reveal that these beneficial T cell populations are activated by damage-associated signals that originate from damaged CNS tissue. Moreover, these T cells secrete IL-4, which promotes neural survival and regrowth through induction of neurotrophin signaling. The results of this study suggest that strategies to increase IL-4-producing T cells in the CNS have therapeutic potential for limiting neuronal damage as the result of trauma, inflammation, or neurodegeneration.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder and is associated with metabolic dysfunction. Persistent hepatic inflammation in diseased livers results in progressive fibrosis and loss of hepatic function. Vascular adhesion protein-1 (VAP-1) is expressed on the hepatic endothelium and recruits leukocytes to the liver; however, it is also produced as a soluble form (sVAP-1) that has monoamine oxidase activity. In this episode, David Adams, Chris Weston, and Emma Shepherd discuss their work, which links sVAP-1 levels in patient serum to NAFLD severity and prognosis. In murine hepatic injury models, loss of VAP-1 or inhibition of VAP-1 enzymatic function reduced inflammatory cell recruitment to the liver and fibrosis. The results of this study suggest that targeting VAP-1 has potential as a therapeutic strategy for limiting hepatic inflammation and fibrosis.
Many lines of evidence support a link between prolonged inflammation and tumorigenic transformation. For example, patients with inflammatory bowel disease are at increased risk of developing colon cancer. In this episode, Julie Saba, Emilie Degagné, and Padmavathi Bandhuvula reveal that dietary sphingolipid metabolism influences intestinal inflammation and carcinogenesis. The results of this study suggest that plant-based sphingolipids have potential as protective agents against colon cancer.
The rare demyelinating disorder progressive multifocal leukoencephalopathy is triggered by JC virus infection of glial cells. Current models to study JC virus infection are limited to cell culture systems due to the human-selective nature of the virus. In this episode, Steve Goldman and colleagues develop a murine model that is permissive to JC virus infection. This study provides an important tool for future evaluation of JC virus pathogenesis and potential therapies.
Binge eating is associated with obesity and depression. This disorder is more prevalent in women, and there is an apparent correlation between low estrogen levels and this behavior. In this episode, Yong Xu, Xuehong Cao, and Pingwen Xu demonstrate that estrogen replacement therapy attenuates binge eating behaviors in ovariectomized mice and that this effect was mediated by the estrogen receptor-α (ERα) in serotonergic neurons of the dorsal raphe nuclei (DRN). Moreover, systemic delivery of a glucagon-like peptide-1–estrogen (GLP-1–estrogen) conjugate, which targets estrogen to GLP-1-expressing regions like the DRN, reduced binge eating in ovariectomized females. The results of this study suggest that ERα in the DRN has potential as therapeutic target for treating binge eating–associated disorders.
Copyright © 2015 American Society for Clinical Investigation