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Research reveals inner workings of immune system 'thermostat'

When bacteria, viruses or parasites attack, immune system cells unleash the soldiers. These "hot" protein compounds kill invaders ?but also trigger inflammation, which, if unchecked, can destroy tissue, induce shock and kill the host. So immune system cells let loose another protein compound to cool down the immune response.

Precisely how this immune system "thermostat" operates is unclear. The leading hypothesis is that these compounds ?which act as furnace and air conditioner ?battle it out over control of the system's inflammatory response.

But new research, led by George Yap of Brown University, shows that these cytokines don't operate independently and in opposition. They operate in harmony and are controlled by the same master. In work published in the Journal of Immunology, Yap and his team show that the "cool" anti-inflammatory protein compound known as Interleukin 10 is activated by Interferon-γ, a class of proteins secreted by a class of white blood cells known as T helper 1 cells. The team then traced secretion of Interferon-γ indirectly to tyrosine kinase 2, or tyk2, the same protein that signals "hot" inflammatory cytokines Interleukin 12 and Interferon-α and Interferon-β.

"Under the prevailing paradigm, scientists believe that the pro- and anti-inflammatory arms of the immune system just antagonize each other," Yap said. "Here we show that they actually induce each other. 'Hot' cytokines don't inhibit 'cool' ones ?they trigger their production. Wounding, in effect, triggers a healing process."

In previous research, Yap discovered that mutant mice with a naturally defective tyk2 gene were immune to arthritis, a condition caused by inflammation. But these mutants were much more susceptible to opportunistic infections. Why? Without tyk2, Yap found, mice didn't make enough of the pro-inflammatory warriors that destroy harmful bugs and cause inflammation. This finding established the notion that tyk2 signaling controlled I
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Source:Brown University


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