Lung allografts are prone to rejection, even though recipients undergo aggressive immunosuppressive therapy. Lymphatic vessels serve as conduits for immune cell trafficking and have been implicated in the mediation of allograft rejection. In this issue of the
Jonathan S. Maltzman, Hasina Outtz Reed, Mark L. Kahn
Immune-suppressive cell populations, including Tregs and suppressor monocytes, have been implicated in long-term survival of allografts in both human transplant recipients and animal models. The factors that drive differentiation and function of these cell populations are not completely understood. In this issue, Bézie and colleagues identify IL-34 as an important mediator of allograft tolerance in a rat model of heart transplantation. Their data support a model in which IL-34 production by Tregs promotes a population of suppressive macrophages that in turn promote Treg differentiation. The results of this study support further exploration of the immunosuppressive properties of IL-34.
James I. Kim, Laurence A. Turka
Glucose stimulation of insulin secretion in pancreatic β cells involves cell depolarization and subsequent opening of voltage-dependent Ca2+ channels to elicit insulin granule exocytosis. This pathway alone does not account for the entire magnitude of the secretory response in β cells. In this issue, Ferdaoussi, Dai, and colleagues reveal that insulin secretion is amplified by cytosolic isocitrate dehydrogenase–dependent transfer of reducing equivalents, which generates NADPH and reduced glutathione, which in turn activates sentrin/SUMO-specific protease-1 (SENP1). β Cell–specific deletion of
Alan D. Attie
Central and peripheral tolerance checkpoints are in place to remove autoreactive B cell populations and prevent the development of autoimmunity. In this issue of the
Jean-Claude Weill, Claude-Agnès Reynaud
Recent gene therapy progress has raised the possibility that vision loss caused by inherited retinal degeneration can be slowed or prevented. Unfortunately, patients are not usually diagnosed until enough degeneration has occurred that the deterioration in vision is noticeable. Therefore, effective gene therapy must halt degeneration to stabilize and preserve any remaining vision. Gene therapy methods currently in human clinical trials rely on subretinal or intravitreal injections of adeno-associated virus to deliver the therapeutic gene. To date, long-term results in patients treated with subretinal injections for Leber congenital amaurosis have been mixed. Proposed limitations include variability in the gene delivery method and a possible point of no return, at which treatment would be ineffective. In this issue of the
James B. Hurley, Jennifer R. Chao
Iron-deficient individuals experience a loss of appetite that can be restored with iron supplementation. It has been proposed that iron influences the satiety hormone leptin; however, a direct link between iron and leptin has remained elusive. In this issue of the
Nancy C. Andrews
B cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common malignancy in children. While treatments have improved remarkably over the past four decades, resistant disease and late effects that result from cytotoxic chemotherapy remain serious problems for individuals with BCP ALL. Improved genetic tools have led to the discovery of numerous somatic mutations associated with BCP ALL, leading to a framework for the genetic classification of BCP ALL. In this issue of the
Terry J. Fry, Peter D. Aplan
HIV-1 infection usually leads to systemic chronic inflammation that is associated with gut microbial translocation. The recently defined group 3 innate lymphoid cells (ILC3s) are critical for maintenance of intestinal barrier function; however, it is not clear whether and how HIV-1 infection influences the function of these cells. In this issue of the
Xiaohuan Guo, Yang-Xin Fu
Hemodynamic forces regulate many aspects of blood vessel disease and development, including susceptibility to atherosclerosis and remodeling of primary blood vessels into a mature vascular network. Vessels of the lymphatic circulatory system are also subjected to fluid flow–associated forces, but the molecular and cellular mechanisms by which these forces regulate the formation and maintenance of lymphatic vessels remains largely uncharacterized. This issue of the
Tsutomu Kume
The mammalian heart contains a population of resident macrophages that expands in response to myocardial infarction through the recruitment of monocytes. Infarct macrophages exhibit high phenotypic diversity and respond to microenvironmental cues by altering their functional properties and secretory profile. In this issue of the
Nikolaos G. Frangogiannis
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