title: Basophils promote innate lymphoid cell responses in inflamed skin.
abstract: Type 2 inflammation underlies allergic diseases such as atopic dermatitis, which is characterized by the accumulation of basophils and group 2 innate lymphoid cells (ILC2s) in inflamed skin lesions. Although murine studies have demonstrated that cutaneous basophil and ILC2 responses are dependent on thymic stromal lymphopoietin, whether these cell populations interact to regulate the development of cutaneous type 2 inflammation is poorly defined. In this study, we identify that basophils and ILC2s significantly accumulate in inflamed human and murine skin and form clusters not observed in control skin. We demonstrate that murine basophil responses precede ILC2 responses and that basophils are the dominant IL-4-enhanced GFP-expressing cell type in inflamed skin. Furthermore, basophils and IL-4 were necessary for the optimal accumulation of ILC2s and induction of atopic dermatitis-like disease. We show that ILC2s express IL-4Rα and proliferate in an IL-4-dependent manner. Additionally, basophil-derived IL-4 was required for cutaneous ILC2 responses in vivo and directly regulated ILC2 proliferation ex vivo. Collectively, these data reveal a previously unrecognized role for basophil-derived IL-4 in promoting ILC2 responses during cutaneous inflammation.
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Brian S
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Kelvin
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Mark C
authors.initials: MC
authors.lastname: Siracusa
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Steven A
authors.initials: SA
authors.lastname: Saenz
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brestoff
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Monticelli
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Mario
authors.initials: M
authors.lastname: Noti
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Elia D
authors.initials: ED
authors.lastname: Tait Wojno
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Fung
authors.affiliation: Laboratory for Cytokine Regulation, Research Center for Integrative Medical Science, RIKEN Yokohama Institute, Kanagawa 230-0045, Japan; Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba 278-0022, Japan; and.
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 dartis@mail.med.upenn.edu.
authors.forename: David
authors.initials: D
authors.lastname: Artis
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D016207:Cytokines; D015847:Interleukin-4; D011956:Receptors, Cell Surface; D000094632:Thymic Stromal Lymphopoietin; C508598:IL4 protein, human; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit