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A novel mechanism that regulates pro-inflammatory cells is identified
Date:8/10/2011

wo transcription factors called FOXO1 and KLF2, which are normally inhibited by PI-3K and Akt activity, suppress the production of Th17 cytokines when overexpressed, even if PI-3K and Akt are fully active. These lines of evidence highlight a novel anti-inflammatory mechanism of action for PI-3K and Akt inhibitors, some of which are in clinical development for cancer-related indications.

"The Th17 subset of T cells have potent weapons. It seems the level of gamma-c cytokines in the local environment acts as a danger signal, it tells Th17 cells to load their weapons and ready to fire if they are triggered by the enemy," said Dr. Unutmaz.

Because of their importance in infectious and autoimmune diseases, the proportion of Th17 cells in the blood of an individual has become a useful biomarker when evaluating autoimmune disease progression or patient responses to treatments. The current method to quantify Th17 cells in blood or tissues involves looking at the secretion of their characteristic cytokines (i.e., IL-17 or IL-22) directly after the cells have been isolated. However, the researchers in this study noticed that this type of "ex vivo" cytokine analysis underestimates the frequency of Th17 cells in the blood of both healthy individuals and rheumatoid arthritis patients. In fact, the majority of human Th17 cells in blood displayed a "poised" phenotype, expressing neither IL-17 nor IL-22 unless they were first stimulated with gamma-c cytokines. This finding has important implications, both for how T cells are classified based on cytokine expression, and how Th17 cells are enumerated in human clinical investigations.

"There are many published studies that have relied on counting human Th17 cells based on their ability to secrete IL-17 out of the blood. We will have to be more careful interpreting these results, since a significant portion of Th17 reserves are not detected by current assays," said Dr. Unutmaz.

The findings in thi
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Contact: Christopher Rucas
christopher.Rucas@nyumc.org
212-404-3525
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

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