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New Cellular Pathway Triggering Allergic Asthma Response Identified

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In a recent article published in the online Early Edition of the Proceedings of the National Academy of Sciences, it has been revealed that researchers at the University of California, San Diego School of Medicine along with collaborators in Korea and Scotland, have discovered a novel signaling pathway critical to the immune response of cells associated with the initiation of allergic asthma. The researchers are of the opinion that the study could point the way to new therapies that could be used to suppress the inflammatory allergic response. This in turn will offer potential relief to millions of Americans who suffer from this chronic lung condition and other such allergic diseases.

The researchers demonstrated that dendritic cells (DC) – a type of white blood cell, which trigger a reduction in the production of cyclic AMP or cAMP, a key messenger molecule for signaling inside cells is involved in T helper 2 (Th2) type inflammation in allergic asthma. It is found that when this gene that codes for a protein that promotes the production of cAMP was deleted in the mouse models, it triggered spontaneous bronchial asthma in them. This symptom has many similarities with human asthma.  When then cAMP levels were increased, it inhibited the cells’ inflammatory response that results in asthma’s characteristic symptoms.

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Eyal Raz, MD, professor of medicine and the study's principal investigator said that their finding and the related mechanism are very different from the current known view of activation of specific T helper cell responses. Co-author Paul Insel, MD, professor of pharmacology and medicine remarked that they were surprised to find the role of cAMP formation and action in dendritic cells in the induction of allergic response. It suggests that this signaling pathway is involved in other immune-related functions as well.

The immune response of humans, mice and other vertebrates comprises of two fundamental components, the first of which is the innate immune system that recognizes and responds to pathogens in an immediate, but generalized, way but does not confer long-lasting immunity. In the second one highly specialized T and B cells eliminate or prevent pathogen growth. They also create immunological memory in case of future encounters with the same pathogen. It is the adaptive immune system.

In the adaptive immune system, Th2 immunity has an important role to play. Th1 responses target intracellular pathogens, such as viruses and bacteria that have invaded host cells. The Th2 response is more effective against extracellular pathogens like bacteria, parasites and toxins that operate outside of cells.

In case of allergic asthma, allergens, such as pet dander, pollen, mold and dust mites are inhaled. Symptoms include inflammation and narrowing of the airways, resulting in wheezing, chest tightness, shortness of breath, coughing, etc. The common form of allergic asthma is associated with an exaggerated Th2 immune response. It is seen that it affects people of all ages; however it is more common in childhood. More than 25 million Americans suffer from the condition.

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Jihyung Lee, PhD, a post-doctoral fellow and first author of the study said that this research will open new avenues for exploration of DC-related molecules as mediators that influence Th2 induction and Th2 ‘bias. In their study, some of these molecules have already been identified and others are under investigation. Hopefully, more will be identified in the near-future.

Raz emphasized that the genetic mouse model developed for the research had multiple similarities with human allergic asthma and that is the reason, they are quite optimistic that the mice will reveal additional novel insights into human allergy which will further fuel their study.