title: IL-13 from intraepithelial lymphocytes regulates tissue homeostasis and protects against carcinogenesis in the skin.
abstract: The skin is under constant renewal and exposure to environmental challenges. How homeostasis is maintained alongside protective mechanisms against damage is unclear. Among the basal epithelial cells (ECs) is a population of resident intraepithelial lymphocytes (IELs) that provide host-protective immune surveillance. Here we show that IELs cross-communicate with ECs via the production of IL-13. Skin ECs are activated by IEL-derived IL-13, enabling a canonical EC stress response. In the absence of IL-13, or canonical IEL, the skin has decreased ability to repair its barrier and increased susceptibility to cutaneous carcinogenesis. IL-13 controls the rate of EC movement through the epidermis, which might explain the importance of IL-13 for epidermal integrity and its suppressive effect on skin carcinogenesis. These findings show that IL-13 acts as a molecular bridge between IELs and ECs, and reveal a critical host-defensive role for type-2 immunity in regulating EC tissue homeostasis and carcinogenesis.
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Dalessandri
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Greg
authors.initials: G
authors.lastname: Crawford
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Hayes
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Rocio
authors.initials: R
authors.lastname: Castro Seoane
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Strid
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology*; D006706:Homeostasis; D018793:Interleukin-13 / Q000502:physiology*; D000067596:Interleukin-33 / Q000378:metabolism; D000075942:Intraepithelial Lymphocytes / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology*; D012878:Skin Neoplasms / Q000209:etiology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C506535:Il33 protein, mouse; D018793:Interleukin-13; D000067596:Interleukin-33; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse