IL-3 in the development and function of basophils |
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Institution: | 1. Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy;2. Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy;3. World Allergy Organization (WAO) Center of Excellence, 80131, Naples, Italy;4. Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131, Naples, Italy;5. Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, Baltimore, MD, 21224, United States |
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Abstract: | The β common chain (βc) cytokine family includes granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and IL-5, all of which use βc as key signaling receptor subunit. GM-CSF, IL-3 and IL-5 have specific roles as hematopoietic growth factors. IL-3 binds with high affinity to the IL-3 receptor α (IL-3Rα/CD123) and then associates with the βc subunit. IL-3 is mainly synthesized by different subsets of T cells, but is also produced by several other immune basophils, dendritic cells (DCs), mast cells, etc.] and non-immune cells (microglia and astrocytes). The IL-3Rα is also expressed by immune (basophils, eosinophils, mast cells, DCs, monocytes, and megacaryocytes) and non-immune cells (endothelial cells and neuronal cells). IL-3 is the most important growth and activating factor for human and mouse basophils, primary effector cells of allergic disorders. IL-3-activated basophils and mast cells are also involved in different chronic inflammatory disorders, infections, and several types of cancer. IL-3 induces the release of cytokines (i.e., IL-4, IL-13, CXCL8) from human basophils and preincubation of basophils with IL-3 potentiates the release of proinflammatory mediators and cytokines from IgE- and C5a-activated basophils. IL-3 synergistically potentiates IL-33-induced mediator release from human basophils. IL-3 plays a pathogenic role in several hematologic cancers and may contribute to autoimmune and cardiac disorders. Several IL-3Rα/CD123 targeting molecules have shown some efficacy in the treatment of hematologic malignancies. |
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Keywords: | Asthma Basophil Cancer GM-CSF IL-3 IL-33 |
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