UCSF Journal Club: Recent research by UCSF scientists
Alexandra Greer
Science Editor
IMMUNOLOGY: ApoE suppresses atherosclerosis by reducing lipid accumulation in circulating monocytes and the expression of inflammatory molecules on monocytes and vascular endothelium. Gaudreault, N. et al., (Raffai). Arteriosclerosis, Thrombosis, and Vascular Biology. Nov 3. [Epub ahead of print]
ApoE, or apolipoprotein E, is a ligand of the low-density lipoprotein receptor (LDR) that helps to lower cholesterol and decrease the risk of atherosclerosis. In addition to its role in lowering cholesterol levels, ApoE has been reported to be an anti-inflammatory – though how it does this has been difficult to study. In this paper, researchers were able to study ApoE’s anti-inflammatory role by crossing ApoE-low mice to LDR-low mice in order to study ApoE’s role independent of the LDR. Interestingly, they found that ApoE lowers the intracellular lipid content of blood monocytes and macrophages. Furthermore, ApoE lowers the numbers of circulating inflammatory cells (including monocytes) and the expression of inflammatory markers on both immune cells and vascular endothelium, indicating that ApoE has a wide variety of functions contributing to the prevention of atherosclerosis.
MICROBIOLOGY: A microRNA derived from an apparent canonical biogenesis pathway regulates variant surface protein gene expression in Giardia lamblia. Saraiya, A.A.; Li, W.; Wang, C.C. RNA. Oct 27. [Epub ahead of print]
Giardia lamblia is a parasite found in many sources of untreated natural water that colonizes the human gut and causes diarrhea, malaise, and other GI symptoms – though about 50% of the time, colonization is asymptomatic. Once it has colonized, Giardia evades our immune system by changing the proteins (or antigens) expressed on its surface (called ‘variant surface proteins’), so that our cells cannot effectively mount an antigen-specific response to infection. Here, researchers have identified a microRNA capable of regulating the expression of variant surface proteins. Unlike other microRNAs in Giardia that have been identified in controlling variant surface proteins, this one in particular seems to be generated through canonical pathways.
IMMUNOLOGY: Autoimmune lymphoproliferative syndrome due to FAS mutations outside the signal transducing death domain: Molecular mechanisms and clinical penetrance. Hsu, A.P. et al., (Puck). Genetics in Medicine. Oct 7. [Epub ahead of print]
During the course of an infection, it is crucial for our immune cells to multiply in order to overwhelm the pathogen and maintain health. After the infection has subsided, it is equally crucial for many of our now ‘expanded’ immune cells to die via apoptosis so we don’t overwhelm ourselves with billions of active, potentially deadly cells. In patients with autoimmune lymphoproliferative syndrome, or ALPS, cells are defective in apoptosis and unintentionally stick around after infections have resolved. This results in multiple forms of autoimmunity and an increased risk of a variety of cancers. Many patients with ALPS have mutations in the FAS receptor’s signaling transduction ‘death domain’ – FAS being nicknamed the ‘death receptor’ because its activation causes an immune cell to die by apoptosis. Here, scientists have identified ALPS patients with a variety of different FAS mutations different from the typical death domain mutations.
IMMUNOLOGY: Loss of MAGT1 abrogates the Mg(2+) flux required for T cell signaling and leads to a novel human primary immunodeficiency. Li, F.Y.; Lenardo, M.J.; Chaigne-Delalande, B. Magnesium Research. 24(3):109-14.
Like neurons, immune cells require changes in ion concentrations to initiate a signaling event. For T-cells, binding of MHC to the T-cell receptor (TCR) causes a surge in intracellular Calcium that promotes activation of transcription factors that then cause production and release of effector molecules. Like Calcium, Magnesium has been shown to play a role in the activation of immune cells, though its exact function has long been controversial. In this paper, researchers have identified a novel type of immunodeficiency that involves a lack of Magnesium flux upon activation of the TCR, while Calcium levels are normal.¬ These patients have a defect in a Magnesium transporter that results in prolonged viral infection and increased risks of some cancers, resulting from an inability to adequately transduce activating signals via Magnesium.
Alexandra Greer is a fourth-year biomedical sciences student.
This article appeared in the November 10, 2011 issue of Synapse.