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Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor
Dietmar M W Zaiss1, Jorg van Loosdregt, Andrea Gorlani
1Department 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.
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