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Immunity. 2013 Feb 21;38(2):275-84. doi: 10.1016/j.immuni.2012.09.023. Epub 2013 Jan 17.

Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor.

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1
Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, University of Utrecht, 3584 CL Utrecht, The Netherlands. d.zaiss@uu.nl

Abstract

Epidermal growth factor receptor (EGFR) is known to be critically involved in tissue development and homeostasis as well as in the pathogenesis of cancer. Here we showed that Foxp3(+) regulatory T (Treg) cells express EGFR under inflammatory conditions. Stimulation with the EGF-like growth factor Amphiregulin (AREG) markedly enhanced Treg cell function in vitro, and in a colitis and tumor vaccination model we showed that AREG was critical for efficient Treg cell function in vivo. In addition, mast cell-derived AREG fully restored optimal Treg cell function. These findings reveal EGFR as a component in the regulation of local immune responses and establish a link between mast cells and Treg cells. Targeting of this immune regulatory mechanism may contribute to the therapeutic successes of EGFR-targeting treatments in cancer patients.

PMID:
23333074
PMCID:
PMC3582723
DOI:
10.1016/j.immuni.2012.09.023
[Indexed for MEDLINE]
Free PMC Article

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