Immunology Advance: Blocking Alarmins to Treat Long-Term Disease

By Adem Lewis / in , , , , , , , , /

My name is Kevin Vannella. I am a research fellow in the Laboratory of Parasitic Diseases. Our focus is on the immune response that gets turned on by tissue injuries caused by allergens that lead to asthma or by parasitic infections in the liver. There’s been a lot of recent interest in the signaling proteins that get made at the start of that immune response called the alarmins. More specifically, IL-25, IL-33, and TSLP. To understand how important they are, we blocked the signaling of each of these alarmins in long-term disease models in mice. In the parasite model, we found that blocking the alarmins individually had no effect. But when we blocked all three of them in combination, we saw a significant improvement. In the asthma model, we also got a really
effective improvement. There was less inflammation. There was less tissue scarring. But that only worked when we started the blockade from the beginning. If we tried to administer the blockade to established asthma, we did not get any improvement in the disease. Recently, there are actually encouraging results in humans that show that blocking TSLP alone can be beneficial. Our results suggest we could
probably reach a broader population of patients by blocking TSLP in addition to IL-33 and IL-25. More work needs to be done to better understand how this could be translated into clinical trials.

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