PMID- 25089660 OWN - NLM STAT- MEDLINE DCOM- 20150226 LR - 20211021 IS - 1523-1747 (Electronic) IS - 0022-202X (Linking) VI - 135 IP - 1 DP - 2015 Jan TI - Basophil-derived amphiregulin is essential for UVB irradiation-induced immune suppression. PG - 222-228 LID - S0022-202X(15)37027-5 [pii] LID - 10.1038/jid.2014.329 [doi] AB - 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. FAU - Meulenbroeks, Chantal AU - Meulenbroeks C AD - Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands. FAU - van Weelden, Huib AU - van Weelden H AD - Department of Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Schwartz, Christian AU - Schwartz C AD - Department of Infection Biology, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. FAU - Voehringer, David AU - Voehringer D AD - Department of Infection Biology, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. FAU - Redegeld, Frank A M AU - Redegeld FAM AD - Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. FAU - Rutten, Victor P M G AU - Rutten VPMG AD - 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. FAU - Willemse, Ton AU - Willemse T AD - 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. FAU - Sijts, Alice J A M AU - Sijts AJAM AD - Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands. FAU - Zaiss, Dietmar M W AU - Zaiss DMW AD - 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. LA - eng GR - 095831/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140704 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (Amphiregulin) RN - 0 (Areg protein, mouse) RN - 0 (EGF Family of Proteins) SB - IM MH - Amphiregulin MH - Animals MH - Basophils/*immunology/metabolism/radiation effects MH - Dermatitis, Contact/immunology/*radiotherapy MH - Disease Models, Animal MH - EGF Family of Proteins/genetics/*immunology/metabolism MH - Female MH - Immune Tolerance/*immunology/*radiation effects MH - Male MH - Mast Cells/immunology/metabolism/radiation effects MH - Mice, Inbred C57BL MH - Mice, Knockout MH - T-Lymphocytes, Regulatory/immunology/metabolism/radiation effects MH - *Ultraviolet Therapy EDAT- 2014/08/05 06:00 MHDA- 2015/02/27 06:00 CRDT- 2014/08/05 06:00 PHST- 2014/05/26 00:00 [received] PHST- 2014/07/25 00:00 [revised] PHST- 2014/07/28 00:00 [accepted] PHST- 2014/08/05 06:00 [entrez] PHST- 2014/08/05 06:00 [pubmed] PHST- 2015/02/27 06:00 [medline] AID - S0022-202X(15)37027-5 [pii] AID - 10.1038/jid.2014.329 [doi] PST - ppublish SO - J Invest Dermatol. 2015 Jan;135(1):222-228. doi: 10.1038/jid.2014.329. Epub 2014 Jul 4.