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Signaling pathways activated by a protease allergen in basophils

Rosenstein, Rachel K., Bezbradica, Jelena S., Yu, Shuang, Medzhitov, Ruslan
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.46 pp. E4963
T-lymphocytes, allergens, basophils, calcium signaling, helminths, immune response, immunologic receptors, models, proteinases, proteolysis
Significance Helminths and allergens stimulate type 2 immune responses by largely unknown mechanisms. Proteolytic activity is a common feature of many helminths and allergens and can promote activation of the immune system. Signaling pathways activated by these proteases remain poorly characterized and are the focus of this study. Using basophils as model type 2 immune cells, we identified roles for the immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor Fc receptor γ-chain and calcium signaling in protease-stimulated basophil activation. We suggest models to explain how protease sensing, ITAM signaling, and nuclear factor of activated T cells pathways contribute to produce allergic type 2 responses. Elucidation of these signaling pathways and ultimately the identity of protease allergen sensors will be important for the development of pharmacologic strategies to target the initiation of allergic responses.