title: Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor.
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.
authors: Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, University of Utrecht, 3584 CL Utrecht, The Netherlands. d.zaiss@uu.nl
authors: Dietmar M W
authors: DM
authors: Zaiss
authors: Jorg
authors: J
authors: van Loosdregt
authors: Andrea
authors: A
authors: Gorlani
authors: Cornelis P J
authors: CP
authors: Bekker
authors: Andrea
authors: A
authors: Gröne
authors: Maria
authors: M
authors: Sibilia
authors: Paul M P
authors: PM
authors: van Bergen en Henegouwen
authors: Rob C
authors: RC
authors: Roovers
authors: Paul J
authors: PJ
authors: Coffer
authors: Alice J A M
authors: AJ
authors: Sijts
mesh_terms: D066258:Amphiregulin; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D066255:EGF Family of Proteins; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D057134:Antibodies, Neutralizing; C587849:Areg protein, mouse; D066255:EGF Family of Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006023:Glycoproteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; C500290:peptide SVYDFFVWL; C064658:RAG-1 protein; C541485:EGFR protein, mouse; D066246:ErbB Receptors