Heart-stopping antibodies

Spred-1 moderates eosinophil activation normally mediated by IL-5, according to a study by Inoue et al. on page 73. Mice lacking Spred-1 have overly exuberant eosinophils and develop exaggerated allergic responses to inhaled antigens. Allergies and asthma are characterized by invasion of the airways by T cells and eosinophils. A subset of CD4 T cells, known as Th2 cells, produce an array of cytokines, including IL-5 and IL-13, which recruit eosinophils to the lung where they release their stores of histamine and other inflammatory proteins. The importance of Th2 cells and their associated cytokines in allergic responses is well established, but less is known about the regulation of eosinophil recruitment and activation. The Spred (Sprouty-related EVH1 domain–containing protein) family of membrane-bound proteins was identified recently by this group and shown to encode negative regulators of Ras–Erk signaling in neuronal cells. The demonstrated importance of the Erk pathway in differentiation of Th2 cells and in eosinophil survival prompted the authors to examine the role of Spred-1 in allergic asthma. Mice lacking Spred-1 developed a more severe allergic reaction due to increased numbers of eosinophils in the lungs. T cells, by contrast, were unaffected by the lack of Spred-1—they were recruited in similar numbers and produced comparable amounts of cytokines in its absence and its presence. The authors attributed the exaggerated eosinophil recruitment to an increased sensitivity to IL-5, since injection of IL-5, but not IL-13, into the lungs of Spred-1–deficient mice caused increased recruitment of eosinophils. IL-5 stimulation of primary eosinophils also resulted in hyperactivation of the Ras–Erk signaling pathway, but not of other signaling pathways. Why a lack of Spred-1 had no effect on Th2 responses is not completely clear, but it may simply reflect the low expression levels of Spred-1 by T cells. Allergic responses (purple) in the lung are increased in Spred-1-deficient mice (bottom). Heart-stopping antibodies