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

BACKGROUND: Amphiregulin, a member of the epidermal growth factor family, is expressed by activated mouse T(H)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.