JCI table of contents: Oct. 5, 2006

Crohn's disease and ulcerative colitis are the most common forms of inflammatory bowel disease (IBD). Although IBD is thought to be caused by an inappropriate immune response to the bacteria living naturally in the gut, exactly how bacteria trigger this response is not known. Now, in a study appearing online on October 5 in advance of publication in the November print issue of the Journal of Clinical Investigation, researchers from the University of Philadelphia have shown that mice lacking the protein RELM-beta are protected from colitis induced by ingestion of dextran sodium sulfate (DSS).

Previous studies have shown that bacteria in the gut induce cells of the intestine to produce RELM-beta. So, David Wu and colleagues set out to investigate whether this protein had a role in IBD. They found that mice lacking RELM-beta were protected from DSS-induced colitis and that RELM-beta was highly expressed in the colon of mice that spontaneously develop an IBD-like disease. As RELM-beta was found to activate macrophages to produce pro-inflammatory factors both in vitro and in vivo, the authors suggest that RELM-beta is one important link between bacteria and the onset of IBD.

TITLE: Absence of bacterially induced RELM-beta reduces injury in the dextran sodium sulfate model of colitis

AUTHOR CONTACT:

Gary D. Wu
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: (215) 898-0158; Fax: (215) 573-2024; E-mail: gdwu@mail.med.upenn.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=28121

Bullous pemphigoid (BP) is a skin disorder of the elderly that is characterized by the presence of fluid-filled blisters on the skin. Individuals with BP have large amounts of antibodies that recognize two of the individual's own proteins (BP180 and BP230), but exactly how these antibodies cause disease has not be determined. Now, in a study using a mouse model of BP, which appears online on October 5 in advance of publication in the November print issue of the Journal of Clinical Investigation, researchers from the University of North Carolina, have shown that these antibodies activate an immune system pathway known as the classical complement pathway.

Transfer of antibodies specific for mouse BP180 to other mice induces the formation of blisters similar to those seen in individuals with BP. However, Zhi Liu and colleagues found that these antibodies do not cause disease in mice lacking C4 (a crucial component of the classical complement pathway). In the absence of activation of the classical complement pathway, immune cells known as mast cells were not activated and neutrophils (another immune cell type) were not recruited to the skin. This study identifies a mechanism by which self-reactive antibodies can cause blister formation in mice, and might lead to new treatments for individuals with BP and other autoimmune blistering diseases, such as herpes gestationis -- which is a nonviral disease of pregnancy.

TITLE: Role of different pathways of the complement cascade in experimental bullous pemphigoid

AUTHOR CONTACT:

Zhi Liu
University of North Carolina, Chapel Hill, North Carolina, USA.
Phone: (919) 966-0788; Fax: (919) 966-3898; E-mail: zhiliu@med.unc.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=17891

Disorders that result from duplication or deletion of large regions of DNA are known as genomic disorders and are relatively common, ~1 per 1,000 births. Each disorder is characterized by a distinct set of neurobehavioral traits. For example, dup(17)(p11.2p11.2) is characterized by, among other things, learning disabilities, attention deficit disorder, and reduced body weight. Although it is known that duplication of a 3.7-Mb region of DNA in chromosome 17 band p11.2 causes dup(17)(p11.2p11.2), it is not known which of the 19 genes in this region is responsible for the dup(17)(p11.2p11.2) characteristics.

In a study appearing online on October 5, in advance of publication in the November print issue of the Journal of Clinical Investigation, James Lupski and colleagues from Baylor College of Medicine, Houston, show that normalizing only the number of copies of the gene Rai1 corrects the reduced body weight and learning defects observed in a mouse model of dup(17)(p11.2p11.2). This study, which indicates that duplication of a single gene -- Rai1 -- can lead to a complex disorder in mice, not only has implications for individuals with dup(17)(p11.2p11.2) but might also shed light on genes that regulate obesity and learning.

TITLE: Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2)

AUTHOR CONTACT:

James R. Lupski
Baylor College of Medicine, Houston, Texas, USA.
Phone: (713) 798-6530; Fax: (713) 798-5073; E-mail: jlupski@bcm.tmc.edu.

Katherina Walz
Centro de Estudios Científicos, Valdivia, Chile.
Phone: +56-63-234514; Fax: +56-63-234517; E-mail: kwalz@cecs.cl.

View the PDF of this article at: https://www.the-jci.org/article.php?id=28953

Viruses use a number of different strategies to escape the host immune response. For example, adenoviruses that infect humans (which most commonly cause respiratory infections) produce several proteins that enable the virus to escape immune responses mediated by the pro-inflammatory soluble factor TNF. One of these proteins, E3-14.7K, inhibits the ability of TNF to cause the virus-infected cell to die. But exactly how it inhibits this process was previously unknown. Now, Stefan Schütze and colleagues from University Hospital of Schleswig-Holstein, Germany, show that expression of E3-14.7K in both human and mouse cells inhibits the internalization of TNF receptor 1 (TNFR1). This in turn prevents TNFR1 recruiting the other proteins it needs to cause the cell to die. Similar retention of TNFR1 at the cell surface was observed in human cells infected with E3-14.7K-expressing adenovirus. This study, which appears online on October 5 in advance of publication in the November print issue of the Journal of Clinical Investigation, describes a new mechanism of viral evasion of the immune response.

TITLE: Inhibition of TNF receptor 1 internalization by adenovirus 14.7K as a novel immune escape mechanism

AUTHOR CONTACT:

Stefan Schütze
University Hospital of Schleswig-Holstein, Kiel, Germany.
Phone: +49-431-597-3382; Fax: +49-431-597-3335; E-mail: schuetze@immunologie.uni-kiel.de.

View the PDF of this article at: https://www.the-jci.org/article.php?id=23771