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

J Allergy Clin Immunol. 2010 Dec;126(6):1260-6.e4. doi: 10.1016/j.jaci.2010.08.040. Epub 2010 Oct 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphiregulin
  • Animals
  • Asthma / blood
  • Asthma / immunology*
  • Basophils / immunology
  • Basophils / metabolism*
  • Basophils / pathology
  • Cell Separation
  • Cells, Cultured
  • EGF Family of Proteins
  • Flow Cytometry
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Glycoproteins / metabolism*
  • Humans
  • Immunization
  • 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
  • Mice
  • Mice, Inbred C57BL
  • Phosphoric Diester Hydrolases / biosynthesis
  • Pyrophosphatases / biosynthesis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology


  • AREG protein, human
  • Amphiregulin
  • Areg protein, mouse
  • EGF Family of Proteins
  • ENPP3 protein, human
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-3
  • Interleukin-3 Receptor alpha Subunit
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases