Human basophils express amphiregulin in response to T cell–derived IL-3

• Published in: Journal of allergy and clinical immunology 2010-12, Vol.126 (6), p.1260-1266.e4
• Main Authors: Qi, Yilin, MSc, Operario, Darwin J., PhD, Oberholzer, Christopher M., MD, Kobie, James J., PhD, Looney, R. John, MD, Georas, Steve N., MD, Mosmann, Tim R., PhD
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Amphiregulin; Animals; Asthma - blood; Asthma - immunology; Basophils; Basophils - immunology; Basophils - metabolism; Basophils - pathology; Biological and medical sciences; Cell Separation; Cells, Cultured; Colleges & universities; Cytokines; EGF Family of Proteins; Epidermal growth factor; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Glycoproteins - genetics; Glycoproteins - immunology; Glycoproteins - metabolism; Humans; IL-3; Immunization; Immunopathology; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - immunology; Intercellular Signaling Peptides and Proteins - metabolism; Interleukin-3 - immunology; Interleukin-3 - metabolism; Interleukin-3 Receptor alpha Subunit - biosynthesis; Kinases; Ligands; Lymphocytes; Medical sciences; Mice; Mice, Inbred C57BL; Nematoda; Phosphoric Diester Hydrolases - biosynthesis; Pyrophosphatases - biosynthesis; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T cell receptors; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2010.08.040

Background Amphiregulin, a member of the epidermal growth factor family, is expressed by activated mouse TH 2 cells. Amphiregulin produced by mouse hematopoietic cells contributes to the elimination of a nematode infection by a type 2 effector response. Objective To identify the human peripheral blood cell population expressing amphiregulin. Methods Amphiregulin-expressing cells were identified by flow cytometry of cell surface markers and histologic staining. Histamine and amphiregulin in supernatants were measured by enzyme immunoassay. Quantitative real-time PCR was used to measure mRNA expression. Results Stimulation of human PBMCs by anti-CD3 + anti-CD28 antibodies induced expression of amphiregulin mRNA and protein by a non–T-cell population. The amphiregulin-producing cells were basophils, as judged by morphology and expression of CD203c and CD123 (IL-3 receptor α chain). Activated mouse basophils also produced amphiregulin. Amphiregulin expression by basophils in response to anti-TCR stimulation required IL-3 produced by T cells, and IL-3 alone induced high levels of amphiregulin expression by purified basophils. Amphiregulin was expressed at much higher levels when human basophils were stimulated by IL-3 than by IgE cross-linking, whereas the opposite was true for IL-4 expression and histamine release. Heparin-binding epidermal growth factor–like growth factor was also expressed by IL-3–stimulated human basophils. PBMCs from human subjects with asthma contained significantly higher numbers of basophils able to produce amphiregulin compared with controls with or without allergy. Conclusion IL-3 can induce basophils to express high levels of amphiregulin, which may contribute to tissue remodeling during type 2 immune responses such as asthma.