Delicate protein balance behind immune system response identified

December 11th, 2007 - 1:15 pm ICT by admin  

Washington, Dec 11 (ANI): Researchers from the University of Pennsylvania School of Veterinary Medicine have identified the protein interactions involved in the immune system process that fights infection, but in certain inflammatory diseases runs amok and attacks friendly tissue.

Led by Christopher Hunter, chair of the Department of Pathobiology at Penn Vet, the research team has identified the pathways that lead to the production of the signalling protein, or cytokine, Interleukin 10 (IL-10) which plays a significant role in regulating the balance between the protective white blood, or T, cell response and one that is pathological and out of control.

IL-10 has long been known as a major anti-inflammatory factor but the events that lead to its production have been poorly understood.

The findings of the study said that messenger proteins Interleukin 27, or a combination of Interleukin 6 and another type of messenger molecule called transforming growth factor beta, induce production of IL-10. These results suggest that modulating these messenger molecules could increase IL-10 concentrations that temper overactive immune responses.

This information sheds new light on the immune-system response and may provide directed means to intervene in severe autoimmune diseases such as colitis, multiple sclerosis and arthritis.

The deeper we delve into the role of cytokines in the immune system response, the more we realize that they are part of an elaborately balanced system kept in check by the conflicting regulatory functions of the cytokines themselves. When combined with the work from our colleagues at Schering Plough, Harvard and Jefferson University, these studies provide new insights into the pathways that can be used to temper autoimmune inflammation, Hunter said.

Although there are many sources of IL-10 in the body, the details of how it is synthesized were poorly understood. Hunters team determined that the process begins with cytokines IL-27 and IL-6 inducing production Th1 , Th2 and Th17 T cells and concludes that cytokines like IL-27 can promote the ability of these cells to produce IL-10. The effect was dependent on the transcription factors STAT1 and STAT3 for IL-27 and on STAT3 for IL-6.

The research team tested this hypothesis by removing the IL-27 receptor from genetically engineered mice. Once infected with disease, the mice were unable to generate T cells producing IL-10.

In previous studies, Penn researchers learned that Interluekin-27 was involved in the immune-system response by limiting the duration and intensity of white blood activation, an “off switch” to the cascade of messenger proteins that serve to further activate the immune system.
Previous to their research, the general assumption among scientists was that IL-27 promoted inflammation. (ANI)

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