title: Basophil-derived amphiregulin is essential for UVB irradiation-induced immune suppression.
abstract: UVB irradiation (290-320 nm) is used to treat skin diseases like psoriasis and atopic dermatitis, and is known to suppress contact hypersensitivity (CHS) reactions in mouse models. Regulatory T cells (Treg cells) have been shown to be responsible for this UVB-induced suppression of CHS. The epidermal growth factor (EGF)-like growth factor amphiregulin (AREG) engages EGFR on Treg cells and, in different disease models, it was shown that mast cell-derived AREG is essential for optimal Treg cell function in vivo. Here we determined whether AREG has a role in UVB-induced, Treg cell-mediated suppression of CHS reactions in the skin. Our data show that AREG is essential for UVB-induced CHS suppression. In contrast to the general assumption, however, mast cells were dispensable for UVB-induced immune suppression, whereas basophil-derived AREG was essential. These data reveal, to our knowledge, a previously unreported function for basophils in the homeostasis of immune responses in the skin. Basophils thus fulfill a dual function: they contribute to the initiation of effective type 2 immune responses and, by enhancing the suppressive capacity of local Treg cell populations, also to local immune regulation in the skin.
authors.affiliation: Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Chantal
authors.initials: C
authors.lastname: Meulenbroeks
authors.affiliation: Department of Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Huib
authors.initials: H
authors.lastname: van Weelden
authors.affiliation: Department of Infection Biology, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schwartz
authors.affiliation: Department of Infection Biology, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
authors.affiliation: Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Frank A M
authors.initials: FAM
authors.lastname: Redegeld
authors.affiliation: Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands; Faculty of Veterinary Science, Department of Veterinary Tropical Diseases, University of Pretoria, Pretoria, South Africa.
authors.forename: Victor P M G
authors.initials: VPMG
authors.lastname: Rutten
authors.affiliation: Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands; Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Willemse
authors.affiliation: Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Alice J A M
authors.initials: AJAM
authors.lastname: Sijts
authors.affiliation: Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands; Ashworth Laboratories, Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK. Electronic address: Dietmar.Zaiss@ed.ac.uk.
authors.forename: Dietmar M W
authors.initials: DMW
authors.lastname: Zaiss
mesh_terms: D066258:Amphiregulin; D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D003877:Dermatitis, Contact / Q000276:immunology / Q000532:radiotherapy*; D004195:Disease Models, Animal; D066255:EGF Family of Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007108:Immune Tolerance / Q000276:immunology* / Q000528:radiation effects*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D014467:Ultraviolet Therapy
chemical_list: D066258:Amphiregulin; C587849:Areg protein, mouse; D066255:EGF Family of Proteins