Public Release: 

Scientists uncover a genetic switch that turns immune responses on and off

New research in yhe FASEB Journal suggests that a novel negative regulator called eye transformer impacts JAK/STAT-signaling pathway response with microbial challenge in fruit flies

Federation of American Societies for Experimental Biology

Scientists are keeping their eye on a new discovery published in the November 2011 print issue of the FASEB Journal (http://www.fasebj.org) that explains what causes some genes to go out of control. Scientists have identified a "cellular switch," called eye transformer, that controls the flow of information from chemical signals outside of the cell to genes in the cell nucleus. This study demonstrates that when eye transformer is turned off, the information pathway it controls (the "JAK/STAT pathway") hyper-activates. Because this pathway exists in humans and is involved in many conditions such as cancer, severe immune deficiencies, autoimmune diseases, and allergies, this discovery reveals a new and potentially important drug target for these conditions.

"We hope that our study will open new horizons for researchers studying mammalian JAK/STAT signaling which eventually leads to better understanding how mammalian JAK/STAT signaling is regulated," said Mika Rämet, Ph.D., co-author of the study from the Institute of Medical Technology at the University of Tampere in Finland. "We hope that this information can be then used in developing better treatments for diseases that are influenced by malfunctioning JAK/STAT signaling."

To make this discovery, Rämet and colleagues "silenced" all of the fruit fly genes one by one using RNAi-based screening methods in cultured Drosophila (fruit fly) cells and then analyzed which genes were important for JAK/STAT signaling. They identified five novel regulators, one of which was a negative regulator of eye transformer that proved to negatively regulate the JAK/STAT response during microbial challenge. Further research showed that suppression of eye transformer expression in the eyes of fruit flies by in vivo RNAi causes hyper-activation of JAK/STAT signaling indicated by drastic eye overgrowth when JAK/STAT signaling was activated.

"We tend to treat immune diseases after the inflammation switch has been turned on," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal and a past president of the American College of Rheumatology. "This study sheds new light on how we might to control diseases like rheumatoid arthritis or lupus by keeping our hands on the switch."

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Receive monthly highlights from the FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal (http://www.fasebj.org) is published by the Federation of the American Societies for Experimental Biology (FASEB). The journal has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century and is the most cited biology journal worldwide according to the Institute for Scientific Information.

FASEB comprises 23 societies with more than 100,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB enhances the ability of scientists and engineers to improve--through their research--the health, well-being and productivity of all people. FASEB's mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

Details:Jenni Kallio, Henna Myllymäki, Juha Grönholm, Morag Armstrong, Leena-Maija Vanha-aho, Leena Mäkinen, Olli Silvennoinen, Susanna Valanne, and Mika Rämet
Eye transformer is a negative regulator of Drosophila JAK/STAT signaling. FASEB J. 2010 24: 4467-4479. DOI: 10.1096/fj.10-162784 ; http://www.fasebj.org/cgi/content/abstract/24/11/4467

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