title: Epidermis instructs skin homing receptor expression in human T cells.
abstract: The localization of memory T cells to human skin is essential for long-term immune surveillance and the maintenance of barrier integrity. Although the mechanisms controlling memory T-cell migration to peripheral tissues are poorly understood, the current paradigm includes the localized secretion of "imprinting" signals from tissue-resident dendritic cells in the draining lymph nodes. Here we show that CCR8 expression by newly activated naive T cells is regulated by skin-specific factor(s) derived primarily from epidermal keratinocytes, thereby providing a mechanism for the preferential expression of CCR8 by skin-resident memory T cells. Importantly, no such effects were observed after coculture with primary cells from skin-unrelated epithelia, including mesothelium and small intestine. The keratinocyte-derived CCR8-inducing factor(s) were soluble, and independent of vitamins A and D. Furthermore, the induction of CCR8 under these conditions correlated with an increase in cutaneous lymphocyte-associated antigen expression. Our findings challenge current tissue homing paradigms, especially those involving CCR10, and emphasize the importance of steady-state epidermis rather than tissue-resident dendritic cells in controlling the localization of memory T cells within human skin.
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: McCully
authors.forename: Kristin
authors.initials: K
authors.lastname: Ladell
authors.forename: Svetlana
authors.initials: S
authors.lastname: Hakobyan
authors.forename: Robert E
authors.initials: RE
authors.lastname: Mansel
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Bernhard
authors.initials: B
authors.lastname: Moser
mesh_terms: D002478:Cells, Cultured; D018920:Coculture Techniques; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D054401:Receptors, CCR8 / Q000276:immunology* / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014801:Vitamin A / Q000276:immunology / Q000378:metabolism; D014807:Vitamin D / Q000276:immunology / Q000378:metabolism
chemical_list: C103330:CCR8 protein, human; D054401:Receptors, CCR8; D016201:Receptors, Lymphocyte Homing; D014801:Vitamin A; D014807:Vitamin D