JCI table of contents: November 16, 2006

November 16, 2006

EDITOR'S PICK: Repair not destruction: a new approach to treating retinopathy

Many diseases of the eye (such as retinopathy of prematurity (ROP) and diabetic retinopathy) that result in loss of vision are the result of the growth of abnormal blood vessels that leak and bleed. Current treatments are designed to prevent the growth of these abnormal blood vessels. However, the authors of a study using a mouse model of retinopathy suggest that an alternative treatment strategy might be to repair these blood vessels so that they do not leak and bleed, causing loss of vision.

In the study, which appears online on November 16 in advance of publication in the December print issue of the Journal of Clinical Investigation, Martin Friedlander and colleagues from The Scripps Research Institute, La Jolla, show that the abnormal blood vessels that grow in the retina of mice exposed to a stimulus that induces retinopathy can be converted to normal blood vessels if the mice are transplanted with adult bone marrow-derived myeloid progenitor cells. Blood vessel repair occurred when the transplanted cells migrated to the eye and became cells known as microglial cells, it also required that the transplanted cells express a protein known as HIF-1-alpha.This study has clinical relevance because it suggests that transplantation of autologous bone marrow-derived progenitor cells might be a viable therapy for the treatment of human diseases that resemble this mouse model of retinopathy, such as ROP.

TITLE: Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy

Martin Friedlander
The Scripps Research Institute, La Jolla, California, USA.
Phone: (858) 784-9138; Fax: (858) 784-9135; E-mail: friedlan@scripps.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=29683

IMMUNOLOGY: Dendritic cells help keep pathogens locked up

Most individuals who become infected with the pathogens that cause diseases such as tuberculosis and listeria clear the pathogens without any trouble. However, some people (including diabetics, women who are pregnant, and individuals infected with HIV) are unable to clear the pathogen. In these individuals the immune system instead tries to contain the pathogen inside structures known as granulomas. Precisely how the granulomas that contain Listeria monocytogenes, the causative agent of listeria, are formed has not been well defined.

In a study appearing online on November 16, in advance of publication in the December print issue of the Journal of Clinical Investigation, Joachim Schultze and colleagues from the University of Cologne, Germany, have shown that human immune cells known as dendritic cells (DCs) form part of the outer wall of granulomas containing L. monocytogenes. Both DCs and macrophages in this part of the wall expressed a protein known as IDO, which has previously been shown to have immunosuppressive effects. Expression of IDO by DCs was induced by the soluble factor TNF-alpha, secreted by DCs in response to being infected with L. monocytogenes. The authors suggest that IDO expression is important for maintaining the integrity of the granulomas by preventing immune cells from responding aggressively and destroying the granuloma. Furthermore, decreased expression of the immunosuppressive factor IDO, and therefore decreased granuloma integrity, might explain why individuals treated with TNF-blocking agents (such as individuals with rheumatoid arthritis) often suffer from severe forms of tuberculosis and listeria.

TITLE: Indoleamine 2,3-dioxygenase-expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection

Joachim L. Schultze
University of Cologne, Cologne, Germany.
Phone: +49-221-478-4489; Fax: +49-221-478-86095; E-mail: Joachim.Schultze@uk-koeln.de.

View the PDF of this article at: https://www.the-jci.org/article.php?id=28996

ONCOLOGY: Identifying new effectors of cancer using RNAi

A subset of non-Hodgkin lymphomas are known as anaplastic large cell lymphomas (ALCLs). Many of these lymphomas are characterized by inappropriate constant activation of a protein known as ALK, but the molecular mechanisms by which constantly active ALK causes cells to become cancerous and to survive long-term are not known. Now, in a study appearing online on November 16 in advance of publication in the December print issue of the Journal of Clinical Investigation, researchers from the University of Turin, Italy, have identified two proteins that are required for ALCL cells to become cancerous and/or to survive long-term. Giorgio Inghirami and colleagues analyzed the genes expressed in ALCL cells before and after blocking the constant activation of ALK, using both an approach known as RNAi and chemical ALK inhibitors. A group of genes controlled by constantly active ALK was identified. Further analysis showed that the pro-survival protein BCL2A1 and the gene regulatory protein CEBPB were required for ALCL cells to become cancerous and/or to survive long-term. This study provides evidence that approaches such as RNAi can be used to identify critical mediators of the cancer process, thereby identifying potential therapeutic targets.

TITLE: Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes

Giorgio Inghirami
University of Turin, Turin, Italy.
Phone: +39-011-633-4623; Fax: +39-011-633-6500; E-mail: giorgio.inghirami@unito.it

Roberto Piva
University of Turin, Turin, Italy.
Phone: +39-011-633-6860; Fax: +39-011-633-6887; E-mail: roberto.piva@unito.it

View the PDF of this article at: https://www.the-jci.org/article.php?id=29401

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