Articles in 2009

A serious complication of blood transfusions is transfusion-related acute lung injury, which can be caused by antibodies in the donor blood that recognize and activate host neutrophils. Andreas Greinacher and his colleagues now determine the molecular identity of the antigen recognized by one of these antibodies, termed human neutrophil alloantigen-3a, as a variant of the choline transporter-like protein-2. This finding opens the door to systematic screening of blood donors and recipients.

Orexin, a neuropeptide best known for its role in arousal and its absence in people with narcolepsy, is also involved in the pathophysiology of panic anxiety disorder.

Sterol metabolism modulates immune responses through liver X receptor activation. Tumors harness this signaling pathway and can escape immunosurveillance by inhibiting dendritic cell migration to tumor-draining lymph nodes.

One of the major challenges of metastasis research is being able to track the fate of individual metastasizing cancer cells over time. Here, Kienast et al. describe an animal model in which multiphoton laser scanning microscopy is used to image the steps involved in the establishment of brain metastasis in vivo. The movement of systemically injected, red fluorescent protein–labeled tumor cells is monitored over several weeks, revealing potential targets for therapy.

The virus HTLV-1 is thought to pass between cells through synapses formed when infected lymphocytes make contact with other T cells. Isabelle Thoulouze and her colleagues uncover an alternative mechanism for the cell-to-cell transmission of this virus. They show that HTLV-1 virions bud at the plasma membrane and are held at the cell surface in structures reminiscent of bacterial biofilms. When infected lymphocytes make contacts with other cells, the adhesive viral assemblies are rapidly transferred to to the surface of the new lymphocyte, from which the virions mediate a new round of infection.

Kwakkenbos et al. describe an in vitro method to generate antibody-secreting B cell lines from human peripheral blood memory B cells by transducing them with retroviral vectors encoding Bcl-6 and Bcl-xL. The approach can be used to stably and simultaneously produce high levels of B cell receptor (BCR) on the cell surface and secreted immunoglobulins, useful for studying BCR signaling and producing antigen-specific antibodies.

The circadian clock controls many aspects of human physiology, and disturbances in circadian rhythms have been linked to cardiovascular disease. Masao Doi et al. now delineate a new pathway by which the circadian clock influences hormone production and blood pressure in mice—clock genes control expression of an aldosterone biosynthetic enzyme, such that increased activity of this enzyme in mice with a disrupted circadian clock may account for the increased aldosterone levels and salt-sensitive hypertension seen in these mice.

Premature infants can suffer from an anatomical defect in which the ductus arteriosus, a blood vessel that connects the pulmonary artery and the aorta during fetal development, fails to close at birth. Katrin Echtler et al. now show that platelets are needed for closure in mice and that reduced platelet function may be clinically relevant: in a retrospective study of preterm human infants, low platelet counts were associated with the presence of an unclosed ductus arteriosus.

Deficiency of the transcription factor HNF-1β results in kidney cyst formation. Marco Pontoglio and his colleagues now show that HNF-1β normally remains bound to condensed chromatin during mitosis to facilitate the rapid expression of key genes involved in cell quiescence post-mitosis. In the absence of HNF-1β, these genes fail to express, and the kidney epithelial cells continue to proliferate, resulting in cysts.

Mutations in NOD2—a bacterial sensor in dendritic cells—and mutations in genes related to autophagosome function have been linked to Crohn's disease. Alison Simmons and her colleagues link these susceptibility genes in a single functional pathway. They show that triggering of NOD2 induces autophagy, resulting in increased bacterial antigen presentation on the surface of the dendritic cell. They also show that this process goes awry in dendritic cells expressing the susceptibility variants from individuals with Crohn's disease.

Behind the news, there are always the newsmakers. Inspired by the high school yearbook tradition, we have rounded up a few such individuals worthy of notice in 2009. Some stepped into the spotlight eagerly, whereas others operated behind the scenes.

A look at stories that fell under the radar in 2009

Lipid accumulation leads to atherosclerosis partly by eliciting lethal levels of cellular stress in macrophages. A signaling pathway that drives such lipid-induced toxicity is now identified. The findings reveal a chaperoning function that might provide the clue needed to rescue this pathogenic effect (pages 1383–1391).

There are many ways to modulate the immune response in a therapeutic setting. Drugs that target the proinflammatory mediator IL-1, for instance, can counteract disease in certain types of inflammatory conditions. But such drugs do not work well for other conditions, such as rheumatoid arthritis and other autoimmune diseases. New clinical studies, examined by Kingston Mills and Aisling Dunne, provide insight into this discrepancy. Another approach that has worked well in mice harnesses the ability of regulatory T cells to dampen the immune response. But one barrier in the way of successful application to people is the ability of such cells to change their character for the worse. Massimo Gadina and John O'Shea take a look at a basic research study that highlights this dilemma and examine what it means for the future of human trials.