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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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Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, University of Utrecht, 3584 CL Utrecht, The Netherlands.


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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