News From The Journal Of Clinical Investigation: Aug. 16, 2010
The lungs of most individuals with cystic fibrosis are colonized by the mold Aspergillus fumigatus. In some this causes a condition known as allergic bronchopulmonary aspergillosis (ABPA), which is characterized by wheezing, lung infiltration by immune cells, and lung scarring, while others remain disease free. A team of researchers, led by Jay Kolls, at Louisiana State University Health Sciences Center, New Orleans, has now compared individuals with cystic fibrosis with and without ABPA and identified an immune signature of ABPA. Specifically, individuals with ABPA exhibited heightened immune responses known as CD4+ Th2 responses and lower levels of vitamin D in the blood. As in vitro addition of vitamin D reduced Th2 responses by CD4+ T cells from patients with ABPA, the authors suggest that vitamin D should be tested for its ability to prevent and/or treat ABPA in individuals with cystic fibrosis.
Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis
INFLAMMATION: The mechanisms of therapeutic control of sepsis
Sepsis is a life-threatening condition characterized by a whole-body inflammatory response. Patients with the most severe forms of sepsis are treated with a recombinant form of the human protein aPC. However, the mechanisms by which it mediates its beneficial effects in these patients are not completely understood. But now, a team of researchers, led by Hartmut Weiler, at the BloodCenter of Wisconsin, Milwaukee, has found that immune cells known as dendritic cells that express the proteins CD8 and EPCR are required for aPC to reduce mortality in a mouse model of lethal sepsis. As discussed by Wolfram Ruf, at The Scripps Research Institute, La Jolla, in an accompanying commentary, these data jive well with other recent studies to indicate that control of innate immune responses is an important effect of aPC therapy in patients with severe sepsis.
Activated protein C targets CD8+ dendritic cells to reduce the mortality of endotoxemia in mice
VASCULAR DISEASE: Keeping genes silent a key to avoiding ANCA disease
One cause of inflammation of the small blood vessels (small-vessel vasculitis) is the presence of antineutrophil cytoplasmic autoantibodies (ANCAs) - immune molecules that target proteins produced by immune cells known as neutrophils and cause neutrophils to attack the walls of small blood vessels. ANCAs only arise when neutrophil proteins are expressed aberrantly. Understanding how neutrophil proteins are aberrantly expressed is key to understanding the disease. Ronald Falk and colleagues, at the University of North Carolina, Chapel Hill, have now provided insight into this by analyzing the genes responsible for generating two of the neutrophil proteins aberrantly expressed in ANCA patients, PR3 and MPO. They found that the PR3 and MPO genes in healthy individuals exhibited modifications consistent with gene silencing and that these modifications were perturbed in individuals with ANCA. They therefore conclude that a lack of gene silencing leads to inappropriate expression of the PR3 and MPO genes in individuals with ANCA.
Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis
Journal of Clinical Investigation