In this video collection, authors of findings published in JCI Insight present personally guided tours of their results. The journal accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
The transmembrane protein GARP serves as a receptor for latent TGF-β, resulting in activation of this cytokine. GARP is expressed on the surface of Tregs, tumors, and platelets and has been implicated in cancer immune invasion. In this episode, Zihai Li and colleagues reveal that the GARP-TGF-β complex is present on activated, but not resting, human and murine B cells. Using multiple murine genetic models, the authors determined that this complex is essential for maintaining immune tolerance and for preventing autoimmune disease. These results support further exploration of B cell GARP as a therapeutic target and possible diagnostic tool.
Sepsis is a life-threatening complication of infection that results in over 250,000 deaths per year in the United States. There is a strong correlation between reduced levels of lymphocytes, such as CD8+ and CD4+ T cells, and increased mortality; therefore, strategies aimed to increase these cells have therapeutic potential. The cytokine IL-7 prevents lymphocyte death, increases lymphocyte proliferation, and has been shown to improve intestinal lymphocyte counts in patients with HIV-1. In this episode, Richard Hotchkiss details the results from a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 in patients with septic shock and severe lymphocytopenia. IL-7 reversed the loss of lymphocytes in septic patients, suggesting that this approach be further explored.
Hepatic stellate cells (HSCs) are key mediators of liver fibrosis; however, the pathways that drive HSC migration, proliferation, and ECM production in response hepatic injury are not fully understood. In this episode, Vijay Shah and colleagues show that mice lacking the scaffold protein synectin are protected from liver fibrosis. This protection associated with down regulation of PDGFR-β and PDGFR-α via distinct synectin-regulated mechanisms, thus identifying synectin as an important mediator of liver fibrosis.