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

November 1, 2010, 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 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 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 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."

More information: 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

Related Stories

Recommended for you

15 new genes identified that shape human faces

February 20, 2018
Researchers from KU Leuven (Belgium) and the universities of Pittsburgh, Stanford, and Penn State have identified 15 genes that determine facial features. The findings were published in Nature Genetics.

New software helps detect adaptive genetic mutations

February 20, 2018
Researchers from Brown University have developed a new method for sifting through genomic data in search of genetic variants that have helped populations adapt to their environments. The technique, dubbed SWIF(r), could be ...

New algorithm can pinpoint mutations favored by natural selection in large sections of the human genome

February 20, 2018
A team of scientists has developed an algorithm that can accurately pinpoint, in large regions of the human genome, mutations favored by natural selection. The finding provides deeper insight into how evolution works, and ...

Highly mutated protein in skin cancer plays central role in skin cell renewal

February 20, 2018
Approximately once a month, our skin completely renews itself. If this highly coordinated process goes awry, it can lead to a variety of skin diseases, ranging from skin cancer to psoriasis. Cells lining such organs as skin ...

Study of smoking and genetics illuminates complexities of blood pressure

February 15, 2018
Analyzing the genetics and smoking habits of more than half a million people has shed new light on the complexities of controlling blood pressure, according to a study led by researchers at Washington University School of ...

New mutation linked to ovarian cancer can be passed down through dad

February 15, 2018
A newly identified mutation, passed down through the X-chromosome, is linked to earlier onset of ovarian cancer in women and prostate cancer in father and sons. Kunle Odunsi, Kevin H. Eng and colleagues at Roswell Park Comprehensive ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

KitchenDancer
not rated yet Dec 04, 2010
It's a detail, but the summary for this article should read that the study was published in November 2010, not November 2011.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.