title: Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma.
abstract: The skin harbors a variety of resident leukocyte subsets that must be tightly regulated to maintain immune homeostasis. Hair follicles are unique structures in the skin that contribute to skin dendritic cell homeostasis through chemokine production. We demonstrate that CD4(+) and CD8(+) skin-resident memory T cells (TRM cells), which are responsible for long-term skin immunity, reside predominantly within the hair follicle epithelium of the unperturbed epidermis. TRM cell tropism for the epidermis and follicles is herein termed epidermotropism. Hair follicle expression of IL-15 was required for CD8(+) TRM cells, and IL-7 for CD8(+) and CD4(+) TRM cells, to exert epidermotropism. A lack of either cytokine in the skin led to impaired hapten-induced contact hypersensitivity responses. In a model of cutaneous T cell lymphoma, epidermotropic CD4(+) TRM lymphoma cell localization depended on the presence of hair follicle-derived IL-7. These findings implicate hair follicle-derived cytokines as regulators of malignant and non-malignant TRM cell tissue residence, and they suggest that the cytokines may be targeted therapeutically in inflammatory skin diseases and lymphoma.
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takeya
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.|Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sugihara
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.identifier: http://orcid.org/0000-0001-6610-1902
authors.initials: H
authors.lastname: Saya
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.|Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Keisuke
authors.identifier: http://orcid.org/0000-0002-7005-3138
authors.initials: K
authors.lastname: Nagao
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D004817:Epidermis / Q000276:immunology*; D018859:Hair Follicle / Q000166:cytology / Q000276:immunology*; D006241:Haptens; D006706:Homeostasis; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology*; D051379:Mice; D012867:Skin / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D006241:Haptens; D019409:Interleukin-15; D015851:Interleukin-7